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Published in: Journal of Neuroinflammation 1/2024

Open Access 01-12-2024 | Alzheimer's Disease | Review

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

Authors: Wendy Balestri, Ruchi Sharma, Victor A. da Silva, Bianca C. Bobotis, Annabel J. Curle, Vandana Kothakota, Farnoosh Kalantarnia, Maria V. Hangad, Mina Hoorfar, Joanne L. Jones, Marie-Ève Tremblay, Jehan J. El-Jawhari, Stephanie M. Willerth, Yvonne Reinwald

Published in: Journal of Neuroinflammation | Issue 1/2024

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Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain’s resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.
Literature
1.
go back to reference Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2014;112:24–49.PubMedCrossRef Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2014;112:24–49.PubMedCrossRef
2.
go back to reference Hennessy E, Griffin EW, Cunningham C. Astrocytes are primed by chronic neurodegeneration to produce exaggerated chemokine and cell infiltration responses to acute stimulation with the cytokines IL-1β and TNF-α. J Neurosci. 2015;35(22):8411–22.PubMedPubMedCentralCrossRef Hennessy E, Griffin EW, Cunningham C. Astrocytes are primed by chronic neurodegeneration to produce exaggerated chemokine and cell infiltration responses to acute stimulation with the cytokines IL-1β and TNF-α. J Neurosci. 2015;35(22):8411–22.PubMedPubMedCentralCrossRef
3.
go back to reference Vedam-Mai V. Harnessing the immune system for the treatment of Parkinson’s disease. Brain Res. 2021;1758: 147308.PubMedCrossRef Vedam-Mai V. Harnessing the immune system for the treatment of Parkinson’s disease. Brain Res. 2021;1758: 147308.PubMedCrossRef
5.
go back to reference Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;10(4): a033118.CrossRef Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;10(4): a033118.CrossRef
6.
go back to reference Cetin S, Knez D, Gobec S, Kos J, Pišlar A. Cell models for Alzheimer’s and Parkinson’s disease: at the interface of biology and drug discovery. Biomed Pharmacother. 2022;149: 112924.PubMedCrossRef Cetin S, Knez D, Gobec S, Kos J, Pišlar A. Cell models for Alzheimer’s and Parkinson’s disease: at the interface of biology and drug discovery. Biomed Pharmacother. 2022;149: 112924.PubMedCrossRef
7.
go back to reference Kim TW, Koo SY, Studer L. Pluripotent stem cell therapies for Parkinson disease: present challenges and future opportunities. Front Cell Dev Biol. 2020;8:729.PubMedPubMedCentralCrossRef Kim TW, Koo SY, Studer L. Pluripotent stem cell therapies for Parkinson disease: present challenges and future opportunities. Front Cell Dev Biol. 2020;8:729.PubMedPubMedCentralCrossRef
9.
go back to reference Shen XN, Niu LD, Wang YJ, Cao XP, Liu Q, Tan L, et al. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry. 2019;90(5):590–8.PubMedCrossRef Shen XN, Niu LD, Wang YJ, Cao XP, Liu Q, Tan L, et al. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry. 2019;90(5):590–8.PubMedCrossRef
10.
go back to reference King E, O’Brien J, Donaghy P, Williams-Gray CH, Lawson RA, Morris CM, et al. Inflammation in mild cognitive impairment due to Parkinson’s disease, Lewy body disease, and Alzheimer’s disease. Int J Geriatr Psychiatry. 2019;34(8):1244–50.PubMedCrossRef King E, O’Brien J, Donaghy P, Williams-Gray CH, Lawson RA, Morris CM, et al. Inflammation in mild cognitive impairment due to Parkinson’s disease, Lewy body disease, and Alzheimer’s disease. Int J Geriatr Psychiatry. 2019;34(8):1244–50.PubMedCrossRef
11.
go back to reference Degerskär ANW, Englund EM. Cause of death in autopsy-confirmed dementia disorders. Eur J Neurol. 2020;27(12):2415–21.PubMedCrossRef Degerskär ANW, Englund EM. Cause of death in autopsy-confirmed dementia disorders. Eur J Neurol. 2020;27(12):2415–21.PubMedCrossRef
12.
go back to reference Centeno EGZ, Cimarosti H, Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol Neurodegener. 2018;13(1):27.PubMedPubMedCentralCrossRef Centeno EGZ, Cimarosti H, Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol Neurodegener. 2018;13(1):27.PubMedPubMedCentralCrossRef
13.
go back to reference Mockett BG, Richter M, Abraham WC, Müller UC. Therapeutic potential of secreted amyloid precursor protein APPsα. Front Mol Neurosci. 2017;10. Mockett BG, Richter M, Abraham WC, Müller UC. Therapeutic potential of secreted amyloid precursor protein APPsα. Front Mol Neurosci. 2017;10.
14.
go back to reference Zaretsky DV, Zaretskaia M. Degradation products of amyloid protein: are they the culprits? Curr Alzheimer Res. 2020;17(10):869–80.PubMedCrossRef Zaretsky DV, Zaretskaia M. Degradation products of amyloid protein: are they the culprits? Curr Alzheimer Res. 2020;17(10):869–80.PubMedCrossRef
15.
go back to reference Rischel EB, Gejl M, Brock B, Rungby J, Gjedde A. In Alzheimer’s disease, amyloid beta accumulation is a protective mechanism that ultimately fails. Alzheimer’s & Dementia. 2022;19(3):771–83.CrossRef Rischel EB, Gejl M, Brock B, Rungby J, Gjedde A. In Alzheimer’s disease, amyloid beta accumulation is a protective mechanism that ultimately fails. Alzheimer’s & Dementia. 2022;19(3):771–83.CrossRef
17.
go back to reference Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1094–9.PubMedCrossRef Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1094–9.PubMedCrossRef
18.
go back to reference Ulland TK, Colonna M. TREM2—a key player in microglial biology and Alzheimer disease. Nat Rev Neurol. 2018;14(11):667–75.PubMedCrossRef Ulland TK, Colonna M. TREM2—a key player in microglial biology and Alzheimer disease. Nat Rev Neurol. 2018;14(11):667–75.PubMedCrossRef
19.
go back to reference Sinsky J, Majerova P, Kovac A, Kotlyar M, Jurisica I, Hanes J. Physiological tau interactome in brain and its link to tauopathies. J Proteome Res. 2020;19(6):2429–42.PubMedCrossRef Sinsky J, Majerova P, Kovac A, Kotlyar M, Jurisica I, Hanes J. Physiological tau interactome in brain and its link to tauopathies. J Proteome Res. 2020;19(6):2429–42.PubMedCrossRef
20.
go back to reference Trojanowski JQ, Shin RW, Schmidt ML, Lee VMY. Relationship between plaques, tangles, and dystrophic processes in Alzheimer’s disease. Neurobiol Aging. 1995;16(3):335–40.PubMedCrossRef Trojanowski JQ, Shin RW, Schmidt ML, Lee VMY. Relationship between plaques, tangles, and dystrophic processes in Alzheimer’s disease. Neurobiol Aging. 1995;16(3):335–40.PubMedCrossRef
21.
go back to reference Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, et al. Alzheimer’s disease susceptibility gene apolipoprotein E (APOE) and blood biomarkers in UK biobank (N = 395,769). Beason-Held L, editor. J Alzheimer’s Dis. 2020;1–11. Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, et al. Alzheimer’s disease susceptibility gene apolipoprotein E (APOE) and blood biomarkers in UK biobank (N = 395,769). Beason-Held L, editor. J Alzheimer’s Dis. 2020;1–11.
22.
go back to reference Van Oostveen WM, De Lange ECM, Orzechowski A. Molecular sciences imaging techniques in Alzheimer’s disease: a review of applications in early diagnosis and longitudinal monitoring. Int J Mol Sci. 2021;22(4):2110.PubMedPubMedCentralCrossRef Van Oostveen WM, De Lange ECM, Orzechowski A. Molecular sciences imaging techniques in Alzheimer’s disease: a review of applications in early diagnosis and longitudinal monitoring. Int J Mol Sci. 2021;22(4):2110.PubMedPubMedCentralCrossRef
23.
go back to reference Sutherland K, Li T, Cao C. Alzheimer’s disease and the immune system. SOJ Neurol. 2015;2(1). Sutherland K, Li T, Cao C. Alzheimer’s disease and the immune system. SOJ Neurol. 2015;2(1).
24.
go back to reference Tan AH, Hor JW, Chong CW, Lim SY. Probiotics for Parkinson’s disease: current evidence and future directions. JGH Open. 2021;5(4):414–9.PubMedCrossRef Tan AH, Hor JW, Chong CW, Lim SY. Probiotics for Parkinson’s disease: current evidence and future directions. JGH Open. 2021;5(4):414–9.PubMedCrossRef
25.
go back to reference Bettcher BM, Tansey MG, Dorothée G, Heneka MT. Peripheral and central immune system crosstalk in Alzheimer disease—a research prospectus. Nat Rev Neurol. 2021;17(11):689–701.PubMedPubMedCentralCrossRef Bettcher BM, Tansey MG, Dorothée G, Heneka MT. Peripheral and central immune system crosstalk in Alzheimer disease—a research prospectus. Nat Rev Neurol. 2021;17(11):689–701.PubMedPubMedCentralCrossRef
26.
go back to reference Piao J, Zabierowski S, Dubose BN, Hill EJ, Navare M, Claros N, et al. Preclinical efficacy and safety of a human embryonic stem cell-derived midbrain dopamine progenitor product, MSK-DA01. Cell Stem Cell. 2021;28(2):217–29.PubMedPubMedCentralCrossRef Piao J, Zabierowski S, Dubose BN, Hill EJ, Navare M, Claros N, et al. Preclinical efficacy and safety of a human embryonic stem cell-derived midbrain dopamine progenitor product, MSK-DA01. Cell Stem Cell. 2021;28(2):217–29.PubMedPubMedCentralCrossRef
27.
go back to reference Qiu B, Bessler N, Figler K, Buchholz MB, Rios AC, Malda J, et al. Bioprinting neural systems to model central nervous system diseases. Adv Funct Mater. 2020;30(44):1910250.PubMedPubMedCentralCrossRef Qiu B, Bessler N, Figler K, Buchholz MB, Rios AC, Malda J, et al. Bioprinting neural systems to model central nervous system diseases. Adv Funct Mater. 2020;30(44):1910250.PubMedPubMedCentralCrossRef
28.
go back to reference Jasmin M, Ahn EH, Voutilainen MH, Fombonne J, Guix C, Viljakainen T, et al. Netrin‐1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson’s disease features. EMBO J. 2020;40(3). Jasmin M, Ahn EH, Voutilainen MH, Fombonne J, Guix C, Viljakainen T, et al. Netrin‐1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson’s disease features. EMBO J. 2020;40(3).
29.
go back to reference Fouke KE, Wegman ME, Weber SA, Brady EB, Román-Vendrell C, Morgan JR. Synuclein regulates synaptic vesicle clustering and docking at a vertebrate synapse. Front Cell Dev Biol. 2021;26:9. Fouke KE, Wegman ME, Weber SA, Brady EB, Román-Vendrell C, Morgan JR. Synuclein regulates synaptic vesicle clustering and docking at a vertebrate synapse. Front Cell Dev Biol. 2021;26:9.
30.
go back to reference Yoo G, Shin YK, Lee NK. The role of α-synuclein in SNARE-mediated synaptic vesicle fusion. J Mol Biol. 2023;435(1):167775.PubMedCrossRef Yoo G, Shin YK, Lee NK. The role of α-synuclein in SNARE-mediated synaptic vesicle fusion. J Mol Biol. 2023;435(1):167775.PubMedCrossRef
31.
go back to reference Li Y, Zhu Z, Chen J, Zhang M, Yang Y, Huang P. Dilated perivascular space in the midbrain may reflect dopamine neuronal degeneration in Parkinson’s disease. Front Aging Neurosci. 2020;12. Li Y, Zhu Z, Chen J, Zhang M, Yang Y, Huang P. Dilated perivascular space in the midbrain may reflect dopamine neuronal degeneration in Parkinson’s disease. Front Aging Neurosci. 2020;12.
32.
go back to reference Oliveira FPM, Walker Z, Walker RWH, Attems J, Castanheira JC, Silva Â, et al. 123I-FP-CIT SPECT in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease: a new quantitative analysis of autopsy confirmed cases. J Neurol Neurosurg Psychiatry. 2021;92(6):662–7.CrossRef Oliveira FPM, Walker Z, Walker RWH, Attems J, Castanheira JC, Silva Â, et al. 123I-FP-CIT SPECT in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease: a new quantitative analysis of autopsy confirmed cases. J Neurol Neurosurg Psychiatry. 2021;92(6):662–7.CrossRef
34.
go back to reference Hatton C, Reeve A, Lax NZ, Blain A, Ng YS, El-Agnaf O, et al. Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies. Acta Neuropathol Commun. 2020;8(1). Hatton C, Reeve A, Lax NZ, Blain A, Ng YS, El-Agnaf O, et al. Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies. Acta Neuropathol Commun. 2020;8(1).
35.
go back to reference Kalia LV, Lang AE. Parkinson’s disease. The Lancet. 2015;386(9996):896–912.CrossRef Kalia LV, Lang AE. Parkinson’s disease. The Lancet. 2015;386(9996):896–912.CrossRef
36.
go back to reference Han JW, Ahn YD, Kim WS, Shin CM, Jeong SJ, Song YS, et al. Psychiatric manifestation in patients with Parkinson’s disease. J Korean Med Sci. 2018;33(47). Han JW, Ahn YD, Kim WS, Shin CM, Jeong SJ, Song YS, et al. Psychiatric manifestation in patients with Parkinson’s disease. J Korean Med Sci. 2018;33(47).
37.
go back to reference Lin WC, Lee PL, Lu CH, Lin CP, Chou KH. Linking stage-specific plasma biomarkers to gray matter atrophy in Parkinson disease. Am J Neuroradiol. 2021;42(8):1444–51.PubMedPubMedCentralCrossRef Lin WC, Lee PL, Lu CH, Lin CP, Chou KH. Linking stage-specific plasma biomarkers to gray matter atrophy in Parkinson disease. Am J Neuroradiol. 2021;42(8):1444–51.PubMedPubMedCentralCrossRef
38.
39.
go back to reference Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain Behav Immun. 2021;97:423–39.PubMedCrossRef Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain Behav Immun. 2021;97:423–39.PubMedCrossRef
40.
go back to reference Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 2022;70(1):173–95.PubMedCrossRef Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 2022;70(1):173–95.PubMedCrossRef
41.
go back to reference Wang S, Sudan R, Peng V, Zhou Y, Du S, Yuede CM, et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell. 2022;185(22):4153-4169.e19.PubMedPubMedCentralCrossRef Wang S, Sudan R, Peng V, Zhou Y, Du S, Yuede CM, et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell. 2022;185(22):4153-4169.e19.PubMedPubMedCentralCrossRef
42.
43.
go back to reference Devanney NA, Stewart AN, Gensel JC. Microglia and macrophage metabolism in CNS injury and disease: the role of immunometabolism in neurodegeneration and neurotrauma. Exp Neurol. 2020;329: 113310.PubMedPubMedCentralCrossRef Devanney NA, Stewart AN, Gensel JC. Microglia and macrophage metabolism in CNS injury and disease: the role of immunometabolism in neurodegeneration and neurotrauma. Exp Neurol. 2020;329: 113310.PubMedPubMedCentralCrossRef
44.
go back to reference Verdon DJ, Mulazzani M, Jenkins MR. Cellular and molecular mechanisms of CD8+ T cell differentiation, dysfunction and exhaustion. Int J Mol Sci. 2020;21(19):7357.PubMedPubMedCentralCrossRef Verdon DJ, Mulazzani M, Jenkins MR. Cellular and molecular mechanisms of CD8+ T cell differentiation, dysfunction and exhaustion. Int J Mol Sci. 2020;21(19):7357.PubMedPubMedCentralCrossRef
45.
go back to reference Rocamora-Reverte L, Melzer FL, Würzner R, Weinberger B. The complex role of regulatory T cells in immunity and aging. Front Immunol. 2021;11. Rocamora-Reverte L, Melzer FL, Würzner R, Weinberger B. The complex role of regulatory T cells in immunity and aging. Front Immunol. 2021;11.
46.
go back to reference Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M, et al. Therapeutic B-cell depletion reverses progression of Alzheimer’s disease. Nat Commun. 2021;12(1):2185.PubMedPubMedCentralCrossRef Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M, et al. Therapeutic B-cell depletion reverses progression of Alzheimer’s disease. Nat Commun. 2021;12(1):2185.PubMedPubMedCentralCrossRef
47.
go back to reference Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimer’s & Dementia. 2018;4(1):575–90. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimer’s & Dementia. 2018;4(1):575–90.
48.
go back to reference Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, et al. Microglia states and nomenclature: a field at its crossroads. Neuron. 2022;110(21):3458–83.PubMedPubMedCentralCrossRef Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, et al. Microglia states and nomenclature: a field at its crossroads. Neuron. 2022;110(21):3458–83.PubMedPubMedCentralCrossRef
49.
go back to reference Gross AL, Walker KA, Moghekar AR, Pettigrew C, Soldan A, Albert MS, et al. Plasma markers of inflammation linked to clinical progression and decline during preclinical AD. Front Aging Neurosci. 2019;11. Gross AL, Walker KA, Moghekar AR, Pettigrew C, Soldan A, Albert MS, et al. Plasma markers of inflammation linked to clinical progression and decline during preclinical AD. Front Aging Neurosci. 2019;11.
50.
go back to reference Morgan AR, Touchard S, Leckey C, O’Hagan C, Nevado-Holgado AJ, et al. Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimer’s & Dementia. 2019;15(6):776–87.CrossRef Morgan AR, Touchard S, Leckey C, O’Hagan C, Nevado-Holgado AJ, et al. Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimer’s & Dementia. 2019;15(6):776–87.CrossRef
51.
go back to reference Shabestari SK, Morabito S, Danhash EP, McQuade A, Sanchez JR, Miyoshi E, et al. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice. Cell Rep. 2022;39(11):110961.PubMedCentralCrossRef Shabestari SK, Morabito S, Danhash EP, McQuade A, Sanchez JR, Miyoshi E, et al. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice. Cell Rep. 2022;39(11):110961.PubMedCentralCrossRef
52.
go back to reference St-Pierre MK, VanderZwaag J, Loewen S, Tremblay MÈ. All roads lead to heterogeneity: the complex involvement of astrocytes and microglia in the pathogenesis of Alzheimer’s disease. Front Cell Neurosci. 2022;16. St-Pierre MK, VanderZwaag J, Loewen S, Tremblay MÈ. All roads lead to heterogeneity: the complex involvement of astrocytes and microglia in the pathogenesis of Alzheimer’s disease. Front Cell Neurosci. 2022;16.
53.
go back to reference Bennett FC, Liddelow SA. Microglia metabolic breakdown drives Alzheimer’s pathology. Cell Metab. 2019;30(3):405–6.PubMedCrossRef Bennett FC, Liddelow SA. Microglia metabolic breakdown drives Alzheimer’s pathology. Cell Metab. 2019;30(3):405–6.PubMedCrossRef
54.
go back to reference De Schepper S, Ge JZ, Crowley G, Ferreira LSS, Garceau D, Toomey CE, et al. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. Nat Neurosci. 2023;26(3):406–15.PubMedPubMedCentral De Schepper S, Ge JZ, Crowley G, Ferreira LSS, Garceau D, Toomey CE, et al. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. Nat Neurosci. 2023;26(3):406–15.PubMedPubMedCentral
55.
go back to reference Bisht K, Sharma KP, Lecours C, Sánchez MG, El Hajj H, Milior G, et al. Dark microglia: a new phenotype predominantly associated with pathological states. Glia. 2016;64(5):826–39.PubMedPubMedCentralCrossRef Bisht K, Sharma KP, Lecours C, Sánchez MG, El Hajj H, Milior G, et al. Dark microglia: a new phenotype predominantly associated with pathological states. Glia. 2016;64(5):826–39.PubMedPubMedCentralCrossRef
56.
57.
go back to reference Yan P, Kim KW, Xiao Q, Ma X, Czerniewski LR, Liu H, et al. Peripheral monocyte-derived cells counter amyloid plaque pathogenesis in a mouse model of Alzheimer’s disease. J Clin Invest. 2022;132(11): e152565.PubMedPubMedCentralCrossRef Yan P, Kim KW, Xiao Q, Ma X, Czerniewski LR, Liu H, et al. Peripheral monocyte-derived cells counter amyloid plaque pathogenesis in a mouse model of Alzheimer’s disease. J Clin Invest. 2022;132(11): e152565.PubMedPubMedCentralCrossRef
58.
go back to reference Munawara U, Catanzaro M, Xu W, Tan C, Hirokawa K, Bosco N, et al. Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer’s disease. Immunity & Ageing. 2021;18(1):29.CrossRef Munawara U, Catanzaro M, Xu W, Tan C, Hirokawa K, Bosco N, et al. Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer’s disease. Immunity & Ageing. 2021;18(1):29.CrossRef
59.
go back to reference Sanchez-Sanchez JL, Giudici KV, Guyonnet S, Delrieu J, Li Y, Bateman RJ, et al. Plasma MCP-1 and changes on cognitive function in community-dwelling older adults. Alzheimer’s Res Ther. 2022;14(1):5.CrossRef Sanchez-Sanchez JL, Giudici KV, Guyonnet S, Delrieu J, Li Y, Bateman RJ, et al. Plasma MCP-1 and changes on cognitive function in community-dwelling older adults. Alzheimer’s Res Ther. 2022;14(1):5.CrossRef
60.
go back to reference Machhi J, Yeapuri P, Lu Y, Foster E, Chikhale R, Herskovitz J, et al. CD4+ effector T cells accelerate Alzheimer’s disease in mice. J Neuroinflammation. 2021;18(1):272.PubMedPubMedCentralCrossRef Machhi J, Yeapuri P, Lu Y, Foster E, Chikhale R, Herskovitz J, et al. CD4+ effector T cells accelerate Alzheimer’s disease in mice. J Neuroinflammation. 2021;18(1):272.PubMedPubMedCentralCrossRef
61.
go back to reference Zhou J, Geng Y, Su T, Wang Q, Ren Y, Zhao J, et al. NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury. Cell Rep. 2022;38(13):110557.PubMedCrossRef Zhou J, Geng Y, Su T, Wang Q, Ren Y, Zhao J, et al. NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury. Cell Rep. 2022;38(13):110557.PubMedCrossRef
62.
go back to reference Batista AF, Rody T, Forny-Germano L, Cerdeiro S, Bellio M, Ferreira ST, et al. Interleukin-1β mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-β oligomers. J Neuroinflammation. 2021;18(1):54.PubMedPubMedCentralCrossRef Batista AF, Rody T, Forny-Germano L, Cerdeiro S, Bellio M, Ferreira ST, et al. Interleukin-1β mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-β oligomers. J Neuroinflammation. 2021;18(1):54.PubMedPubMedCentralCrossRef
63.
go back to reference Plescher M, Seifert G, Hansen JN, Bedner P, Steinhäuser C, Halle A. Plaque-dependent morphological and electrophysiological heterogeneity of microglia in an Alzheimer’s disease mouse model. Glia. 2018;66(7):1464–80.PubMedCrossRef Plescher M, Seifert G, Hansen JN, Bedner P, Steinhäuser C, Halle A. Plaque-dependent morphological and electrophysiological heterogeneity of microglia in an Alzheimer’s disease mouse model. Glia. 2018;66(7):1464–80.PubMedCrossRef
64.
go back to reference Franco-Bocanegra DK, Gourari Y, McAuley C, Chatelet DS, Johnston DA, Nicoll JAR, et al. Microglial morphology in Alzheimer’s disease and after Aβ immunotherapy. Sci Rep. 2021;11(1):15955.PubMedPubMedCentralCrossRef Franco-Bocanegra DK, Gourari Y, McAuley C, Chatelet DS, Johnston DA, Nicoll JAR, et al. Microglial morphology in Alzheimer’s disease and after Aβ immunotherapy. Sci Rep. 2021;11(1):15955.PubMedPubMedCentralCrossRef
65.
go back to reference Lee WJ, Liao YC, Wang YF, Lin IF, Wang SJ, Fuh JL. Plasma MCP-1 and cognitive decline in patients with Alzheimer’s disease and mild cognitive impairment: a two-year follow-up study. Sci Rep. 2018;8(1):1280.PubMedPubMedCentralCrossRef Lee WJ, Liao YC, Wang YF, Lin IF, Wang SJ, Fuh JL. Plasma MCP-1 and cognitive decline in patients with Alzheimer’s disease and mild cognitive impairment: a two-year follow-up study. Sci Rep. 2018;8(1):1280.PubMedPubMedCentralCrossRef
66.
go back to reference Dai L, Wang Q, Lv X, Gao F, Chen Z, Shen Y. Elevated β-secretase 1 expression mediates CD4+ T cell dysfunction via PGE2 signalling in Alzheimer’s disease. Brain Behav Immun. 2021;98:337–48.PubMedCrossRef Dai L, Wang Q, Lv X, Gao F, Chen Z, Shen Y. Elevated β-secretase 1 expression mediates CD4+ T cell dysfunction via PGE2 signalling in Alzheimer’s disease. Brain Behav Immun. 2021;98:337–48.PubMedCrossRef
67.
go back to reference Unger MS, Li E, Scharnagl L, Poupardin R, Altendorfer B, Mrowetz H, et al. CD8+ T-cells infiltrate Alzheimer’s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice. Brain Behav Immun. 2020;89:67–86.PubMedCrossRef Unger MS, Li E, Scharnagl L, Poupardin R, Altendorfer B, Mrowetz H, et al. CD8+ T-cells infiltrate Alzheimer’s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice. Brain Behav Immun. 2020;89:67–86.PubMedCrossRef
68.
go back to reference Williams-Gray CH, Foltynie T, Brayne CEG, Robbins TW, Barker RA. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain. 2007;130(7):1787–98.PubMedCrossRef Williams-Gray CH, Foltynie T, Brayne CEG, Robbins TW, Barker RA. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain. 2007;130(7):1787–98.PubMedCrossRef
69.
go back to reference Williams-Gray CH, Mason SL, Evans JR, Foltynie T, Brayne C, Robbins TW, et al. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry. 2013;84(11):1258–64.PubMedCrossRef Williams-Gray CH, Mason SL, Evans JR, Foltynie T, Brayne C, Robbins TW, et al. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry. 2013;84(11):1258–64.PubMedCrossRef
70.
go back to reference Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW, et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain. 2009;132(11):2958–69.PubMedCrossRef Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW, et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain. 2009;132(11):2958–69.PubMedCrossRef
71.
go back to reference Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42(9):781–5.PubMedPubMedCentralCrossRef Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42(9):781–5.PubMedPubMedCentralCrossRef
72.
go back to reference Hill-Burns EM, Factor SA, Zabetian CP, Thomson G, Payami H. Evidence for more than one Parkinson’s disease-associated variant within the HLA region. PLoS ONE. 2011;6(11): e27109.PubMedPubMedCentralCrossRef Hill-Burns EM, Factor SA, Zabetian CP, Thomson G, Payami H. Evidence for more than one Parkinson’s disease-associated variant within the HLA region. PLoS ONE. 2011;6(11): e27109.PubMedPubMedCentralCrossRef
73.
go back to reference Pierce S, Coetzee GA. Parkinson’s disease-associated genetic variation is linked to quantitative expression of inflammatory genes. PLoS ONE. 2017;12(4): e0175882.PubMedPubMedCentralCrossRef Pierce S, Coetzee GA. Parkinson’s disease-associated genetic variation is linked to quantitative expression of inflammatory genes. PLoS ONE. 2017;12(4): e0175882.PubMedPubMedCentralCrossRef
74.
go back to reference Witoelar A, Jansen IE, Wang Y, Desikan RS, Gibbs JR, Blauwendraat C, et al. Genome-wide pleiotropy between Parkinson disease and autoimmune diseases. JAMA Neurol. 2017;74(7):780.PubMedPubMedCentralCrossRef Witoelar A, Jansen IE, Wang Y, Desikan RS, Gibbs JR, Blauwendraat C, et al. Genome-wide pleiotropy between Parkinson disease and autoimmune diseases. JAMA Neurol. 2017;74(7):780.PubMedPubMedCentralCrossRef
75.
go back to reference Li M, Wan J, Xu Z, Tang B. The association between Parkinson’s disease and autoimmune diseases: a systematic review and meta-analysis. Front Immunol. 2023;14:1103053.PubMedPubMedCentralCrossRef Li M, Wan J, Xu Z, Tang B. The association between Parkinson’s disease and autoimmune diseases: a systematic review and meta-analysis. Front Immunol. 2023;14:1103053.PubMedPubMedCentralCrossRef
76.
go back to reference Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022;22(11):657–73.PubMedPubMedCentralCrossRef Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022;22(11):657–73.PubMedPubMedCentralCrossRef
77.
go back to reference Awogbindin IO, Ishola IO, St-Pierre MK, Carrier M, Savage JC, Di Paolo T, et al. Remodeling microglia to a protective phenotype in Parkinson’s disease? Neurosci Lett. 2020;735: 135164.PubMedCrossRef Awogbindin IO, Ishola IO, St-Pierre MK, Carrier M, Savage JC, Di Paolo T, et al. Remodeling microglia to a protective phenotype in Parkinson’s disease? Neurosci Lett. 2020;735: 135164.PubMedCrossRef
78.
go back to reference De Biase LM, Schuebel KE, Fusfeld ZH, Jair K, Hawes IA, Cimbro R, et al. Local cues establish and maintain region-specific phenotypes of basal ganglia microglia. Neuron. 2017;95(2):341–56.PubMedPubMedCentralCrossRef De Biase LM, Schuebel KE, Fusfeld ZH, Jair K, Hawes IA, Cimbro R, et al. Local cues establish and maintain region-specific phenotypes of basal ganglia microglia. Neuron. 2017;95(2):341–56.PubMedPubMedCentralCrossRef
79.
go back to reference Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ. 2014;21(3):369–80.PubMedCrossRef Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ. 2014;21(3):369–80.PubMedCrossRef
80.
go back to reference Smajić S, Prada-Medina CA, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C, et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain. 2022;145(3):964–78.PubMedCrossRef Smajić S, Prada-Medina CA, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C, et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain. 2022;145(3):964–78.PubMedCrossRef
81.
go back to reference Kouli A, Camacho M, Allinson K, Williams-Gray CH. Neuroinflammation and protein pathology in Parkinson’s disease dementia. Acta Neuropathol Commun. 2020;8:1–19.CrossRef Kouli A, Camacho M, Allinson K, Williams-Gray CH. Neuroinflammation and protein pathology in Parkinson’s disease dementia. Acta Neuropathol Commun. 2020;8:1–19.CrossRef
82.
go back to reference Chaudhuri KR, Schapira AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464–74.PubMedCrossRef Chaudhuri KR, Schapira AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464–74.PubMedCrossRef
83.
go back to reference Pellegrini C, D’Antongiovanni V, Miraglia F, Rota L, Benvenuti L, Di Salvo C, et al. Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson’s disease before brain pathology. NPJ Parkinsons Dis. 2022;8(1):9.PubMedPubMedCentralCrossRef Pellegrini C, D’Antongiovanni V, Miraglia F, Rota L, Benvenuti L, Di Salvo C, et al. Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson’s disease before brain pathology. NPJ Parkinsons Dis. 2022;8(1):9.PubMedPubMedCentralCrossRef
84.
go back to reference Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature. 2017;546(7660):656–61.PubMedPubMedCentralCrossRef Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature. 2017;546(7660):656–61.PubMedPubMedCentralCrossRef
85.
go back to reference Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L, et al. Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients. Acta Neuropathol. 2014;128:651–63. Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L, et al. Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients. Acta Neuropathol. 2014;128:651–63.
86.
go back to reference Williams-Gray CH, Wijeyekoon R, Yarnall AJ, Lawson RA, Breen DP, Evans JR, et al. Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE-PD). Mov Disord. 2016;31(7):995–1003.PubMedPubMedCentralCrossRef Williams-Gray CH, Wijeyekoon R, Yarnall AJ, Lawson RA, Breen DP, Evans JR, et al. Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE-PD). Mov Disord. 2016;31(7):995–1003.PubMedPubMedCentralCrossRef
87.
go back to reference Chen X, Hu Y, Cao Z, Liu Q, Cheng Y. Cerebrospinal fluid inflammatory cytokine aberrations in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis: a systematic review and meta-analysis. Front Immunol. 2018;9:2122.PubMedPubMedCentralCrossRef Chen X, Hu Y, Cao Z, Liu Q, Cheng Y. Cerebrospinal fluid inflammatory cytokine aberrations in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis: a systematic review and meta-analysis. Front Immunol. 2018;9:2122.PubMedPubMedCentralCrossRef
88.
go back to reference Yan Z, Yang W, Wei H, Dean MN, Standaert DG, Cutter GR, et al. Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurol Neuroimmunol Neuroinflamm. 2021;8(5). Yan Z, Yang W, Wei H, Dean MN, Standaert DG, Cutter GR, et al. Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurol Neuroimmunol Neuroinflamm. 2021;8(5).
89.
go back to reference Contaldi E, Magistrelli L, Comi C. T lymphocytes in Parkinson’s disease. J Parkinson’s Dis. 2022;12(s1):S65–74.CrossRef Contaldi E, Magistrelli L, Comi C. T lymphocytes in Parkinson’s disease. J Parkinson’s Dis. 2022;12(s1):S65–74.CrossRef
90.
go back to reference Shalash A, Salama M, Makar M, Roushdy T, Elrassas HH, Mohamed W, et al. Elevated serum α-synuclein autoantibodies in patients with Parkinson’s disease relative to Alzheimer’s disease and controls. Front Neurol. 2017;8:720.PubMedPubMedCentralCrossRef Shalash A, Salama M, Makar M, Roushdy T, Elrassas HH, Mohamed W, et al. Elevated serum α-synuclein autoantibodies in patients with Parkinson’s disease relative to Alzheimer’s disease and controls. Front Neurol. 2017;8:720.PubMedPubMedCentralCrossRef
91.
go back to reference Li R, Tropea TF, Baratta LR, Zuroff L, Diaz-Ortiz ME, Zhang B, et al. Abnormal B-cell and Tfh-cell profiles in patients with Parkinson disease: a cross-sectional study. Neurol Neuroimmunol Neuroinflamm. 2022;9(2). Li R, Tropea TF, Baratta LR, Zuroff L, Diaz-Ortiz ME, Zhang B, et al. Abnormal B-cell and Tfh-cell profiles in patients with Parkinson disease: a cross-sectional study. Neurol Neuroimmunol Neuroinflamm. 2022;9(2).
92.
go back to reference Wang P, Luo M, Zhou W, Jin X, Xu Z, Yan S, et al. Global characterization of peripheral B cells in Parkinson’s disease by single-cell RNA and BCR sequencing. Front Immunol. 2022;13: 814239.PubMedPubMedCentralCrossRef Wang P, Luo M, Zhou W, Jin X, Xu Z, Yan S, et al. Global characterization of peripheral B cells in Parkinson’s disease by single-cell RNA and BCR sequencing. Front Immunol. 2022;13: 814239.PubMedPubMedCentralCrossRef
94.
go back to reference Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. The Lancet. 2021;397(10284):1577–90.CrossRef Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. The Lancet. 2021;397(10284):1577–90.CrossRef
95.
go back to reference Khachaturian ZS. The ‘aducanumab story’: will the last chapter spell the end of the ‘amyloid hypothesis’ or mark a new beginning? J Prevent Alzheimer’s Dis. 2022;9(2):190–2. Khachaturian ZS. The ‘aducanumab story’: will the last chapter spell the end of the ‘amyloid hypothesis’ or mark a new beginning? J Prevent Alzheimer’s Dis. 2022;9(2):190–2.
96.
go back to reference Baruch K, Kertser A, Matalon O, Forsht O, Braiman S, Shochat E, et al. IBC-Ab002, an anti-PD-L1 monoclonal antibody tailored for treating Alzheimer’s disease. Alzheimer’s & Dementia. 2020;16(S9): e042978.CrossRef Baruch K, Kertser A, Matalon O, Forsht O, Braiman S, Shochat E, et al. IBC-Ab002, an anti-PD-L1 monoclonal antibody tailored for treating Alzheimer’s disease. Alzheimer’s & Dementia. 2020;16(S9): e042978.CrossRef
97.
go back to reference Kang BW, Kim F, Cho JY, Kim SY, Rhee J, Choung JJ. Phosphodiesterase 5 inhibitor mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions. Alzheimer’s Res Ther. 2022;14(1):1–17. Kang BW, Kim F, Cho JY, Kim SY, Rhee J, Choung JJ. Phosphodiesterase 5 inhibitor mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions. Alzheimer’s Res Ther. 2022;14(1):1–17.
98.
go back to reference Koh SH, Kwon HS, Choi SH, Jeong JH, Na HR, Lee CN, et al. Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer’s disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial. Alzheimer’s Res Ther. 2021;13(1):1–11. Koh SH, Kwon HS, Choi SH, Jeong JH, Na HR, Lee CN, et al. Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer’s disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial. Alzheimer’s Res Ther. 2021;13(1):1–11.
99.
go back to reference Kaeberlein M, Galvan V. Rapamycin and Alzheimer’s disease: time for a clinical trial? Sci Transl Med. 2019;11(476). Kaeberlein M, Galvan V. Rapamycin and Alzheimer’s disease: time for a clinical trial? Sci Transl Med. 2019;11(476).
100.
go back to reference McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;2019(3):1–446. McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;2019(3):1–446.
101.
go back to reference Nørgaard CH, Friedrich S, Hansen CT, Gerds T, Ballard C, Møller DV, et al. Treatment with glucagon‐like peptide‐1 receptor agonists and incidence of dementia: data from pooled double‐blind randomized controlled trials and nationwide disease and prescription registers. Alzheimer’s & Dementia. 2022;8(1). Nørgaard CH, Friedrich S, Hansen CT, Gerds T, Ballard C, Møller DV, et al. Treatment with glucagon‐like peptide‐1 receptor agonists and incidence of dementia: data from pooled double‐blind randomized controlled trials and nationwide disease and prescription registers. Alzheimer’s & Dementia. 2022;8(1).
102.
go back to reference Hua X, Church K, Walker W, L’Hostis P, Viardot G, Danjou P, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the positive modulator of HGF/MET, fosgonimeton, in healthy volunteers and subjects with Alzheimer’s disease: randomized, placebo-controlled, double-blind, phase I clinical trial. J Alzheimer’s Dis. 2022;86(3):1399.CrossRef Hua X, Church K, Walker W, L’Hostis P, Viardot G, Danjou P, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the positive modulator of HGF/MET, fosgonimeton, in healthy volunteers and subjects with Alzheimer’s disease: randomized, placebo-controlled, double-blind, phase I clinical trial. J Alzheimer’s Dis. 2022;86(3):1399.CrossRef
105.
go back to reference Mehanna R, Bajwa JA, Fernandez H, Wagle Shukla AA, others. Cognitive impact of deep brain stimulation on Parkinson’s disease patients. Parkinson’s Dis. 2017;2017. Mehanna R, Bajwa JA, Fernandez H, Wagle Shukla AA, others. Cognitive impact of deep brain stimulation on Parkinson’s disease patients. Parkinson’s Dis. 2017;2017.
106.
go back to reference Stoker TB, Barker RA. Recent developments in the treatment of Parkinson’s disease. F1000Res. 2020;9:862.CrossRef Stoker TB, Barker RA. Recent developments in the treatment of Parkinson’s disease. F1000Res. 2020;9:862.CrossRef
107.
go back to reference Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology. 2021;1(190): 108352.CrossRef Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology. 2021;1(190): 108352.CrossRef
108.
go back to reference van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.PubMedCrossRef van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.PubMedCrossRef
110.
go back to reference Larkin HD. Lecanemab gains FDA approval for early Alzheimer disease. JAMA. 2023;329(5):363–363.PubMed Larkin HD. Lecanemab gains FDA approval for early Alzheimer disease. JAMA. 2023;329(5):363–363.PubMed
111.
go back to reference Tolar M, Abushakra S, Hey JA, Porsteinsson A, Sabbagh M. Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther. 2020;12(1). Tolar M, Abushakra S, Hey JA, Porsteinsson A, Sabbagh M. Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther. 2020;12(1).
113.
go back to reference Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: an update. J Cent Nerv Syst Dis. 2020;29:12. Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: an update. J Cent Nerv Syst Dis. 2020;29:12.
114.
go back to reference Tran TN, Vo TNN, Frei K, Truong DD. Levodopa-induced dyskinesia: clinical features, incidence, and risk factors. J Neural Transm. 2018;125:1109–17.PubMedCrossRef Tran TN, Vo TNN, Frei K, Truong DD. Levodopa-induced dyskinesia: clinical features, incidence, and risk factors. J Neural Transm. 2018;125:1109–17.PubMedCrossRef
115.
go back to reference Turcano P, Mielke MM, Bower JH, Parisi JE, Cutsforth-Gregory JK, Ahlskog JE, et al. Levodopa-induced dyskinesia in Parkinson disease: a population-based cohort study. Neurology. 2018;91(24):e2238–43.PubMedPubMedCentralCrossRef Turcano P, Mielke MM, Bower JH, Parisi JE, Cutsforth-Gregory JK, Ahlskog JE, et al. Levodopa-induced dyskinesia in Parkinson disease: a population-based cohort study. Neurology. 2018;91(24):e2238–43.PubMedPubMedCentralCrossRef
116.
go back to reference Carbone F, Djamshidian A, Seppi K, Poewe W. Apomorphine for Parkinson’s disease: efficacy and safety of current and new formulations. CNS Drugs. 2019;33(9):905–18.PubMedPubMedCentralCrossRef Carbone F, Djamshidian A, Seppi K, Poewe W. Apomorphine for Parkinson’s disease: efficacy and safety of current and new formulations. CNS Drugs. 2019;33(9):905–18.PubMedPubMedCentralCrossRef
117.
go back to reference Khalifeh M, Read MI, Barreto GE, Sahebkar A. Trehalose against Alzheimer’s disease: insights into a potential therapy. BioEssays. 2020;42(8):1900195.CrossRef Khalifeh M, Read MI, Barreto GE, Sahebkar A. Trehalose against Alzheimer’s disease: insights into a potential therapy. BioEssays. 2020;42(8):1900195.CrossRef
118.
go back to reference Jin LW, Di LJ, Nguyen HM, Singh V, Singh L, Chavez M, et al. Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer’s disease. Ann Clin Transl Neurol. 2019;6(4):723–38.PubMedPubMedCentralCrossRef Jin LW, Di LJ, Nguyen HM, Singh V, Singh L, Chavez M, et al. Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer’s disease. Ann Clin Transl Neurol. 2019;6(4):723–38.PubMedPubMedCentralCrossRef
119.
go back to reference Cummings J, Lee G, Nahed P, Kambar MEZN, Zhong K, Fonseca J, et al. Alzheimer’s disease drug development pipeline: 2022. Alzheimer’s and Dementia. 2022;8(1). Cummings J, Lee G, Nahed P, Kambar MEZN, Zhong K, Fonseca J, et al. Alzheimer’s disease drug development pipeline: 2022. Alzheimer’s and Dementia. 2022;8(1).
120.
go back to reference Patel AG, Nehete PN, Krivoshik SR, Pei X, Cho EL, Nehete BP, et al. Innate immunity stimulation via CpG oligodeoxynucleotides ameliorates Alzheimer’s disease pathology in aged squirrel monkeys. Brain. 2021;144(7):2146.PubMedPubMedCentralCrossRef Patel AG, Nehete PN, Krivoshik SR, Pei X, Cho EL, Nehete BP, et al. Innate immunity stimulation via CpG oligodeoxynucleotides ameliorates Alzheimer’s disease pathology in aged squirrel monkeys. Brain. 2021;144(7):2146.PubMedPubMedCentralCrossRef
121.
go back to reference Wang YL, Zhang Y, Xu J. Sodium oligomannate combined with rivastigmine may improve cerebral blood flow and cognitive impairment following CAR-T cell therapy: a case report. Front Oncol. 2022;18:12. Wang YL, Zhang Y, Xu J. Sodium oligomannate combined with rivastigmine may improve cerebral blood flow and cognitive impairment following CAR-T cell therapy: a case report. Front Oncol. 2022;18:12.
122.
go back to reference Potter H, Woodcock JH, Boyd TD, Coughlan CM, O’Shaughnessy JR, Borges MT, et al. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer’s disease. Alzheimer’s & Dementia. 2021;7(1): e12158. Potter H, Woodcock JH, Boyd TD, Coughlan CM, O’Shaughnessy JR, Borges MT, et al. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer’s disease. Alzheimer’s & Dementia. 2021;7(1): e12158.
123.
go back to reference Ward M, Long H, Schwabe T, Rhinn H, Tassi I, Salazar SV, et al. A phase 1 study of AL002 in healthy volunteers. Alzheimer’s & Dementia. 2021;17(S9): e054669.CrossRef Ward M, Long H, Schwabe T, Rhinn H, Tassi I, Salazar SV, et al. A phase 1 study of AL002 in healthy volunteers. Alzheimer’s & Dementia. 2021;17(S9): e054669.CrossRef
124.
go back to reference Torres-Acosta N, O’Keefe JH, O’Keefe EL, Isaacson R, Small G. Therapeutic potential of TNF-α inhibition for Alzheimer’s disease prevention. J Alzheimer’s Dis. 2020;78(2):619.CrossRef Torres-Acosta N, O’Keefe JH, O’Keefe EL, Isaacson R, Small G. Therapeutic potential of TNF-α inhibition for Alzheimer’s disease prevention. J Alzheimer’s Dis. 2020;78(2):619.CrossRef
125.
go back to reference MacPherson KP, Sompol P, Kannarkat GT, Chang J, Sniffen L, Wildner ME, et al. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol Dis. 2017;1(102):81.CrossRef MacPherson KP, Sompol P, Kannarkat GT, Chang J, Sniffen L, Wildner ME, et al. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol Dis. 2017;1(102):81.CrossRef
126.
go back to reference Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 1992;43(4):329–39.PubMedCrossRef Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 1992;43(4):329–39.PubMedCrossRef
127.
go back to reference Labanieh L, Majzner RG, Mackall CL. Programming CAR-T cells to kill cancer. Nat Biomed Eng. 2018;2(6):377–91.PubMedCrossRef Labanieh L, Majzner RG, Mackall CL. Programming CAR-T cells to kill cancer. Nat Biomed Eng. 2018;2(6):377–91.PubMedCrossRef
128.
go back to reference Nickerson P, Jeffery J, Rush D. Long-term allograft surveillance: the role of protocol biopsies. Curr Opin Urol. 2001;11(2):133–7.PubMedCrossRef Nickerson P, Jeffery J, Rush D. Long-term allograft surveillance: the role of protocol biopsies. Curr Opin Urol. 2001;11(2):133–7.PubMedCrossRef
129.
go back to reference Candini O, Grisendi G, Foppiani EM, Brogli M, Aramini B, Masciale V, et al. A novel 3D in vitro platform for pre-clinical investigations in drug testing, gene therapy, and immuno-oncology. Sci Rep. 2019;9(1):1–12.CrossRef Candini O, Grisendi G, Foppiani EM, Brogli M, Aramini B, Masciale V, et al. A novel 3D in vitro platform for pre-clinical investigations in drug testing, gene therapy, and immuno-oncology. Sci Rep. 2019;9(1):1–12.CrossRef
130.
go back to reference Jin Z, Li X, Zhang X, Desousa P, Xu T, Wu A. Engineering the fate and function of human T-Cells via 3D bioprinting. Biofabrication. 2021;13(3): 035016.CrossRef Jin Z, Li X, Zhang X, Desousa P, Xu T, Wu A. Engineering the fate and function of human T-Cells via 3D bioprinting. Biofabrication. 2021;13(3): 035016.CrossRef
131.
go back to reference Gray JI, Westerhof LM, MacLeod MKL. The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination. Immunology. 2018;154(4):574–81.PubMedPubMedCentralCrossRef Gray JI, Westerhof LM, MacLeod MKL. The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination. Immunology. 2018;154(4):574–81.PubMedPubMedCentralCrossRef
132.
go back to reference Snow AL, Oliveira JB, Zheng L, Dale JK, Fleisher TA, Lenardo MJ. Critical role for BIM in T cell receptor restimulation-induced death. Biol Direct. 2008;3(1):1–17.CrossRef Snow AL, Oliveira JB, Zheng L, Dale JK, Fleisher TA, Lenardo MJ. Critical role for BIM in T cell receptor restimulation-induced death. Biol Direct. 2008;3(1):1–17.CrossRef
133.
go back to reference Leach DG, Young S, Hartgerink JD. Advances in immunotherapy delivery from implantable and injectable biomaterials. Acta Biomater. 2019;1(88):15–31.CrossRef Leach DG, Young S, Hartgerink JD. Advances in immunotherapy delivery from implantable and injectable biomaterials. Acta Biomater. 2019;1(88):15–31.CrossRef
134.
go back to reference Lu W, Wei Y, Cao Y, Xiao X, Li Q, Lyu H, et al. CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease. Cancer Immunol Immunother. 2021;70(12):3501–11.PubMedPubMedCentralCrossRef Lu W, Wei Y, Cao Y, Xiao X, Li Q, Lyu H, et al. CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease. Cancer Immunol Immunother. 2021;70(12):3501–11.PubMedPubMedCentralCrossRef
135.
go back to reference Goodridge JP, Reiser JW, Bjordahl R, Mandal M, Chang C, Clarck R, et al. Combinational strategy targeting B cell malignancy using iPSC engineered CAR-NK (FT596) and CAR-T cell (FT819) platforms with therapeutic antibody to achieve an effective deep and durable response. Cancer Res. 2020;80(16_Supplement):2216–2216.CrossRef Goodridge JP, Reiser JW, Bjordahl R, Mandal M, Chang C, Clarck R, et al. Combinational strategy targeting B cell malignancy using iPSC engineered CAR-NK (FT596) and CAR-T cell (FT819) platforms with therapeutic antibody to achieve an effective deep and durable response. Cancer Res. 2020;80(16_Supplement):2216–2216.CrossRef
136.
go back to reference Egrilmez MY, Karabay U, Aydemir S, Baykara B, Husemoglu RB. The cellular responses of human macrophages seeded on 3D printed thermoplastic polyurethane scaffold. J Med Innovat Technol. 2021;3(2):40–5.CrossRef Egrilmez MY, Karabay U, Aydemir S, Baykara B, Husemoglu RB. The cellular responses of human macrophages seeded on 3D printed thermoplastic polyurethane scaffold. J Med Innovat Technol. 2021;3(2):40–5.CrossRef
137.
go back to reference Xiao J, Gao Y. The manufacture of 3D printing of medical grade TPU. Prog Addit Manuf. 2017;2(3):117–23.CrossRef Xiao J, Gao Y. The manufacture of 3D printing of medical grade TPU. Prog Addit Manuf. 2017;2(3):117–23.CrossRef
138.
go back to reference Huang X, He C, Lin G, Lu L, Xing K, Hua X, et al. Induced CD10 expression during monocyte-to-macrophage differentiation identifies a unique subset of macrophages in pancreatic ductal adenocarcinoma. Biochem Biophys Res Commun. 2020;524(4):1064–71.PubMedCrossRef Huang X, He C, Lin G, Lu L, Xing K, Hua X, et al. Induced CD10 expression during monocyte-to-macrophage differentiation identifies a unique subset of macrophages in pancreatic ductal adenocarcinoma. Biochem Biophys Res Commun. 2020;524(4):1064–71.PubMedCrossRef
139.
go back to reference Aldrich A, Kuss MA, Duan B, Kielian T. 3D bioprinted scaffolds containing viable macrophages and antibiotics promote clearance of Staphylococcus aureus craniotomy-associated biofilm infection. ACS Appl Mater Interfaces. 2019;11(13):12298–307.PubMedPubMedCentralCrossRef Aldrich A, Kuss MA, Duan B, Kielian T. 3D bioprinted scaffolds containing viable macrophages and antibiotics promote clearance of Staphylococcus aureus craniotomy-associated biofilm infection. ACS Appl Mater Interfaces. 2019;11(13):12298–307.PubMedPubMedCentralCrossRef
140.
go back to reference Lefebvre M, Jacqueline C, Amador G, Le Mabecque V, Miegeville A, Potel G, et al. Efficacy of daptomycin combined with rifampicin for the treatment of experimental methicillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis. Int J Antimicrob Agents. 2010;36(6):542–4.PubMedCrossRef Lefebvre M, Jacqueline C, Amador G, Le Mabecque V, Miegeville A, Potel G, et al. Efficacy of daptomycin combined with rifampicin for the treatment of experimental methicillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis. Int J Antimicrob Agents. 2010;36(6):542–4.PubMedCrossRef
141.
go back to reference Woitschach F, Kloss M, Schlodder K, Borck A, Grabow N, Reisinger EC, et al. In vitro study of the interaction of innate immune cells with liquid silicone rubber coated with Zwitterionic methyl methacrylate and thermoplastic polyurethanes. Materials. 2021;14(20):5972.PubMedPubMedCentralCrossRef Woitschach F, Kloss M, Schlodder K, Borck A, Grabow N, Reisinger EC, et al. In vitro study of the interaction of innate immune cells with liquid silicone rubber coated with Zwitterionic methyl methacrylate and thermoplastic polyurethanes. Materials. 2021;14(20):5972.PubMedPubMedCentralCrossRef
142.
go back to reference de Medeiros LM, De Bastiani MA, Rico EP, Schonhofen P, Pfaffenseller B, Wollenhaupt-Aguiar B, et al. Cholinergic differentiation of human neuroblastoma SH-SY5Y cell line and its potential use as an in vitro model for Alzheimer’s disease studies. Mol Neurobiol. 2019;56(11):7355–67.PubMedCrossRef de Medeiros LM, De Bastiani MA, Rico EP, Schonhofen P, Pfaffenseller B, Wollenhaupt-Aguiar B, et al. Cholinergic differentiation of human neuroblastoma SH-SY5Y cell line and its potential use as an in vitro model for Alzheimer’s disease studies. Mol Neurobiol. 2019;56(11):7355–67.PubMedCrossRef
143.
go back to reference Gan L, Cookson MR, Petrucelli L, La Spada AR. Converging pathways in neurodegeneration, from genetics to mechanisms. Nat Neurosci. 2018;21(10):1300–9.PubMedPubMedCentralCrossRef Gan L, Cookson MR, Petrucelli L, La Spada AR. Converging pathways in neurodegeneration, from genetics to mechanisms. Nat Neurosci. 2018;21(10):1300–9.PubMedPubMedCentralCrossRef
144.
145.
go back to reference Zhao J, Liu X, Xia W, Zhang Y, Wang C. Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front Mol Neurosci. 2020;4:13. Zhao J, Liu X, Xia W, Zhang Y, Wang C. Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front Mol Neurosci. 2020;4:13.
146.
go back to reference Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener. 2017;12(1):1–11.CrossRef Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener. 2017;12(1):1–11.CrossRef
147.
go back to reference Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, et al. Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS ONE. 2013;8(5): e63862.PubMedPubMedCentralCrossRef Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, et al. Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS ONE. 2013;8(5): e63862.PubMedPubMedCentralCrossRef
148.
go back to reference Brown DG, Wobst HJ. Opportunities and challenges in phenotypic screening for neurodegenerative disease research. J Med Chem. 2019;63(5):1823–40.PubMedCrossRef Brown DG, Wobst HJ. Opportunities and challenges in phenotypic screening for neurodegenerative disease research. J Med Chem. 2019;63(5):1823–40.PubMedCrossRef
149.
go back to reference Cooper O, Hargus G, Deleidi M, Blak A, Osborn T, Marlow E, et al. Differentiation of human ES and Parkinson’s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid. Mol Cell Neurosci. 2010;45(3):258–66.PubMedPubMedCentralCrossRef Cooper O, Hargus G, Deleidi M, Blak A, Osborn T, Marlow E, et al. Differentiation of human ES and Parkinson’s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid. Mol Cell Neurosci. 2010;45(3):258–66.PubMedPubMedCentralCrossRef
150.
go back to reference Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci. 2010;107(36):15921–6.PubMedPubMedCentralCrossRef Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci. 2010;107(36):15921–6.PubMedPubMedCentralCrossRef
151.
go back to reference Ochalek A, Szczesna K, Petazzi P, Kobolak J, Dinnyes A. Generation of cholinergic and dopaminergic interneurons from human pluripotent stem cells as a relevant tool for in vitro modeling of neurological disorders and therapy. Stem Cells Int. 2016;2016. Ochalek A, Szczesna K, Petazzi P, Kobolak J, Dinnyes A. Generation of cholinergic and dopaminergic interneurons from human pluripotent stem cells as a relevant tool for in vitro modeling of neurological disorders and therapy. Stem Cells Int. 2016;2016.
152.
go back to reference Agholme L, Lindström T, Kågedal K, Marcusson J, Hallbeck M. An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J Alzheimer’s Dis. 2010;20(4):1069–82.CrossRef Agholme L, Lindström T, Kågedal K, Marcusson J, Hallbeck M. An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J Alzheimer’s Dis. 2010;20(4):1069–82.CrossRef
153.
go back to reference Hossini AM, Megges M, Prigione A, Lichtner B, Toliat MR, Wruck W, et al. Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer’s disease donor as a model for investigating AD-associated gene regulatory networks. BMC Genomics. 2015;16:1–22. Hossini AM, Megges M, Prigione A, Lichtner B, Toliat MR, Wruck W, et al. Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer’s disease donor as a model for investigating AD-associated gene regulatory networks. BMC Genomics. 2015;16:1–22.
154.
go back to reference Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira AI, Herland A. A 3D Alzheimer’s disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2014;35(5):1420–8.PubMedCrossRef Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira AI, Herland A. A 3D Alzheimer’s disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2014;35(5):1420–8.PubMedCrossRef
155.
go back to reference Choi SH, Kim YH, Quinti L, Tanzi RE, Kim DY. 3D culture models of Alzheimer’s disease: a road map to a “cure-in-a-dish.” Mol Neurodegener. 2016;11:1–11.CrossRef Choi SH, Kim YH, Quinti L, Tanzi RE, Kim DY. 3D culture models of Alzheimer’s disease: a road map to a “cure-in-a-dish.” Mol Neurodegener. 2016;11:1–11.CrossRef
156.
go back to reference Sharma NS, Karan A, Lee D, Yan Z, Xie J. Advances in modeling Alzheimer’s disease in vitro. Adv Nanobiomed Res. 2021;1(12):2100097.CrossRef Sharma NS, Karan A, Lee D, Yan Z, Xie J. Advances in modeling Alzheimer’s disease in vitro. Adv Nanobiomed Res. 2021;1(12):2100097.CrossRef
157.
go back to reference Lee HK, Velazquez Sanchez C, Chen M, Morin PJ, Wells JM, Hanlon EB, et al. Three dimensional human neuro-spheroid model of Alzheimer’s disease based on differentiated induced pluripotent stem cells. PLoS ONE. 2016;11(9): e0163072.PubMedPubMedCentralCrossRef Lee HK, Velazquez Sanchez C, Chen M, Morin PJ, Wells JM, Hanlon EB, et al. Three dimensional human neuro-spheroid model of Alzheimer’s disease based on differentiated induced pluripotent stem cells. PLoS ONE. 2016;11(9): e0163072.PubMedPubMedCentralCrossRef
158.
go back to reference Hernández-Sapiéns MA, Reza-Zaldívar EE, Cevallos RR, Márquez-Aguirre AL, Gazarian K, Canales-Aguirre AA. A three-dimensional Alzheimer’s disease cell culture model using iPSC-derived neurons carrying A246E mutation in PSEN1. Front Cell Neurosci. 2020;14:151.PubMedPubMedCentralCrossRef Hernández-Sapiéns MA, Reza-Zaldívar EE, Cevallos RR, Márquez-Aguirre AL, Gazarian K, Canales-Aguirre AA. A three-dimensional Alzheimer’s disease cell culture model using iPSC-derived neurons carrying A246E mutation in PSEN1. Front Cell Neurosci. 2020;14:151.PubMedPubMedCentralCrossRef
159.
go back to reference Lomoio S, Pandey RS, Rouleau N, Menicacci B, Kim W, Cantley WL, et al. 3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer’s disease. Mol Psychiatry. 2023;1–12. Lomoio S, Pandey RS, Rouleau N, Menicacci B, Kim W, Cantley WL, et al. 3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer’s disease. Mol Psychiatry. 2023;1–12.
160.
go back to reference Kwak SS, Washicosky KJ, Brand E, Von Maydell D, Aronson J, Kim S, et al. Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease. Nat Commun. 2020;11(1):1377.PubMedPubMedCentralCrossRef Kwak SS, Washicosky KJ, Brand E, Von Maydell D, Aronson J, Kim S, et al. Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease. Nat Commun. 2020;11(1):1377.PubMedPubMedCentralCrossRef
161.
go back to reference Taylor-Whiteley TR, Le Maitre CL, Duce JA, Dalton CF, Smith DP. Recapitulating Parkinson’s disease pathology in a three-dimensional human neural cell culture model. Dis Model Mech. 2019;12(4):dmm038042.PubMedPubMedCentralCrossRef Taylor-Whiteley TR, Le Maitre CL, Duce JA, Dalton CF, Smith DP. Recapitulating Parkinson’s disease pathology in a three-dimensional human neural cell culture model. Dis Model Mech. 2019;12(4):dmm038042.PubMedPubMedCentralCrossRef
162.
go back to reference Moreno EL, Hachi S, Hemmer K, Trietsch SJ, Baumuratov AS, Hankemeier T, et al. Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture. Lab Chip. 2015;15(11):2419–28.PubMedCrossRef Moreno EL, Hachi S, Hemmer K, Trietsch SJ, Baumuratov AS, Hankemeier T, et al. Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture. Lab Chip. 2015;15(11):2419–28.PubMedCrossRef
163.
go back to reference Fiore NJ, Ganat YM, Devkota K, Batorsky R, Lei M, Lee K, et al. Bioengineered models of Parkinson’s disease using patient-derived dopaminergic neurons exhibit distinct biological profiles in a 3D microenvironment. Cell Mol Life Sci. 2022;79(2):1–20.CrossRef Fiore NJ, Ganat YM, Devkota K, Batorsky R, Lei M, Lee K, et al. Bioengineered models of Parkinson’s disease using patient-derived dopaminergic neurons exhibit distinct biological profiles in a 3D microenvironment. Cell Mol Life Sci. 2022;79(2):1–20.CrossRef
164.
go back to reference Abdelrahman S, Alsanie WF, Khan ZN, Albalawi HI, Felimban RI, Moretti M, et al. A Parkinson’s disease model composed of 3D bioprinted dopaminergic neurons within a biomimetic peptide scaffold. Biofabrication. 2022;14(4): 044103.CrossRef Abdelrahman S, Alsanie WF, Khan ZN, Albalawi HI, Felimban RI, Moretti M, et al. A Parkinson’s disease model composed of 3D bioprinted dopaminergic neurons within a biomimetic peptide scaffold. Biofabrication. 2022;14(4): 044103.CrossRef
165.
go back to reference Saylam E, Akkaya Y, Ilhan E, Cesur S, Guler E, Sahin A, et al. Levodopa-loaded 3D-printed poly (Lactic) acid/chitosan neural tissue scaffold as a promising drug delivery system for the treatment of Parkinson’s disease. Appl Sci. 2021;11(22):10727.CrossRef Saylam E, Akkaya Y, Ilhan E, Cesur S, Guler E, Sahin A, et al. Levodopa-loaded 3D-printed poly (Lactic) acid/chitosan neural tissue scaffold as a promising drug delivery system for the treatment of Parkinson’s disease. Appl Sci. 2021;11(22):10727.CrossRef
166.
go back to reference Cuní-López C, Quek H, Oikari LE, Stewart R, Nguyen TH, Sun Y, et al. 3D models of Alzheimer’s disease patient microglia recapitulate disease phenotype and show differential drug responses compared to 2D. bioRxiv. 2021;2021–3. Cuní-López C, Quek H, Oikari LE, Stewart R, Nguyen TH, Sun Y, et al. 3D models of Alzheimer’s disease patient microglia recapitulate disease phenotype and show differential drug responses compared to 2D. bioRxiv. 2021;2021–3.
167.
go back to reference Sabate-Soler S, Louise Nickels S, Saraiva C, Berger E, Dubonyte U, Barmpa K, et al. Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality. Wiley Online Library. 2022;70(7):1267–88. Sabate-Soler S, Louise Nickels S, Saraiva C, Berger E, Dubonyte U, Barmpa K, et al. Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality. Wiley Online Library. 2022;70(7):1267–88.
168.
go back to reference Markus B, Anna-Sophie S, Simon G, Dominik L, Alice K, Marvin R, et al. Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies. Altex. 2020;37(3):409–28. Markus B, Anna-Sophie S, Simon G, Dominik L, Alice K, Marvin R, et al. Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies. Altex. 2020;37(3):409–28.
169.
go back to reference Xu R, Boreland AJ, Li X, Erickson C, Jin M, Atkins C, et al. Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology. Stem Cell Reports. 2021;16(8):1923–37.PubMedPubMedCentralCrossRef Xu R, Boreland AJ, Li X, Erickson C, Jin M, Atkins C, et al. Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology. Stem Cell Reports. 2021;16(8):1923–37.PubMedPubMedCentralCrossRef
170.
go back to reference Song L, Yuan X, Jones Z, Vied C, Miao Y, Marzano M, et al. Functionalization of brain region-specific spheroids with isogenic microglia-like cells. Sci Rep. 2019;9(1). Song L, Yuan X, Jones Z, Vied C, Miao Y, Marzano M, et al. Functionalization of brain region-specific spheroids with isogenic microglia-like cells. Sci Rep. 2019;9(1).
171.
go back to reference Cai H, Ao Z, Hu L, Moon Y, Wu Z, Lu HC, et al. Acoustofluidic assembly of 3D neurospheroids to model Alzheimer’s disease. Analyst. 2020;145(19):6243–53.PubMedPubMedCentralCrossRef Cai H, Ao Z, Hu L, Moon Y, Wu Z, Lu HC, et al. Acoustofluidic assembly of 3D neurospheroids to model Alzheimer’s disease. Analyst. 2020;145(19):6243–53.PubMedPubMedCentralCrossRef
172.
go back to reference Ilaria R, Marta T, Gianluigi F, Diego A, Carmen G. 3D brain tissue physiological model with co-cultured primary neurons and glial cells in hydrogels. J Tissue Eng. 2020;11:1–13. Ilaria R, Marta T, Gianluigi F, Diego A, Carmen G. 3D brain tissue physiological model with co-cultured primary neurons and glial cells in hydrogels. J Tissue Eng. 2020;11:1–13.
173.
go back to reference Chemmarappally JM, Pegram HCN, Abeywickrama N, Fornari E, Hargreaves AJ, De Girolamo LA, et al. A co-culture nanofibre scaffold model of neural cell degeneration in relevance to Parkinson’s disease. Sci Rep. 2020;10(1):1–14.CrossRef Chemmarappally JM, Pegram HCN, Abeywickrama N, Fornari E, Hargreaves AJ, De Girolamo LA, et al. A co-culture nanofibre scaffold model of neural cell degeneration in relevance to Parkinson’s disease. Sci Rep. 2020;10(1):1–14.CrossRef
174.
go back to reference Rueda-Gensini L, Serna JA, Rubio D, Camilo Orozco J, Bolaños NI, Cruz JC, et al. Three-dimensional neuroimmune co-culture system for modeling Parkinson’s disease microenvironments in vitro. Biofabrication. 2023;15:45001.CrossRef Rueda-Gensini L, Serna JA, Rubio D, Camilo Orozco J, Bolaños NI, Cruz JC, et al. Three-dimensional neuroimmune co-culture system for modeling Parkinson’s disease microenvironments in vitro. Biofabrication. 2023;15:45001.CrossRef
175.
go back to reference Drummond E, Wisniewski T. Alzheimer’s disease: experimental models and reality. Acta Neuropathol. 2017;133(2):155–75.PubMedCrossRef Drummond E, Wisniewski T. Alzheimer’s disease: experimental models and reality. Acta Neuropathol. 2017;133(2):155–75.PubMedCrossRef
176.
go back to reference Sundaramoorthy TH, Castanho I. The Neuroepigenetic landscape of vertebrate and invertebrate models of neurodegenerative diseases. Epigenet Insights. 2022;4:15. Sundaramoorthy TH, Castanho I. The Neuroepigenetic landscape of vertebrate and invertebrate models of neurodegenerative diseases. Epigenet Insights. 2022;4:15.
177.
go back to reference Fernandez-Funez P, de Mena L, Rincon-Limas DE. Modeling the complex pathology of Alzheimer’s disease in Drosophila. Exp Neurol. 2015;1(274):58–71.CrossRef Fernandez-Funez P, de Mena L, Rincon-Limas DE. Modeling the complex pathology of Alzheimer’s disease in Drosophila. Exp Neurol. 2015;1(274):58–71.CrossRef
178.
go back to reference Alexander AG, Marfil V, Li C. Use of C. elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases. Front Genet. 2014;5:95895.CrossRef Alexander AG, Marfil V, Li C. Use of C. elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases. Front Genet. 2014;5:95895.CrossRef
179.
go back to reference Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/Cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.PubMedCrossRef Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/Cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.PubMedCrossRef
180.
go back to reference Tassetto M, Kunitomi M, Andino R. Circulating immune cells mediate a systemic RNAi-based adaptive antiviral response in drosophila. Cell. 2017;169(2):314-325.e13.PubMedPubMedCentralCrossRef Tassetto M, Kunitomi M, Andino R. Circulating immune cells mediate a systemic RNAi-based adaptive antiviral response in drosophila. Cell. 2017;169(2):314-325.e13.PubMedPubMedCentralCrossRef
181.
go back to reference Dhankhar J, Agrawal N, Shrivastava A. An interplay between immune response and neurodegenerative disease progression: an assessment using Drosophila as a model. J Neuroimmunol. 2020;15(346): 577302.CrossRef Dhankhar J, Agrawal N, Shrivastava A. An interplay between immune response and neurodegenerative disease progression: an assessment using Drosophila as a model. J Neuroimmunol. 2020;15(346): 577302.CrossRef
182.
go back to reference Nagai J, Yu X, Papouin T, Cheong E. Behaviorally consequential astrocytic regulation of neural circuits. Neuron. 2021;109(4):576–96.PubMedCrossRef Nagai J, Yu X, Papouin T, Cheong E. Behaviorally consequential astrocytic regulation of neural circuits. Neuron. 2021;109(4):576–96.PubMedCrossRef
183.
go back to reference Sarparast M, Hinman J, Pourmand E, Vonarx D, Ramirez L, Ma W, et al. Cytochrome P450 and epoxide hydrolase metabolites in Aβ and tau-induced neurodegeneration: insights from Caenorhabditis elegans. bioRxiv. 2023;2023.10.02.560527. Sarparast M, Hinman J, Pourmand E, Vonarx D, Ramirez L, Ma W, et al. Cytochrome P450 and epoxide hydrolase metabolites in Aβ and tau-induced neurodegeneration: insights from Caenorhabditis elegans. bioRxiv. 2023;2023.10.02.560527.
184.
go back to reference Stewart CR, Stuart LM, Wilkinson K, Van Gils JM, Deng J, Halle A, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11(2):155.PubMedCrossRef Stewart CR, Stuart LM, Wilkinson K, Van Gils JM, Deng J, Halle A, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11(2):155.PubMedCrossRef
185.
go back to reference Tan L, Schedl P, Song HJ, Garza D, Konsolaki M. The Toll–>NFkappaB signaling pathway mediates the neuropathological effects of the human Alzheimer’s Abeta42 polypeptide in Drosophila. PLoS ONE. 2008;3(12):e3966.PubMedPubMedCentralCrossRef Tan L, Schedl P, Song HJ, Garza D, Konsolaki M. The Toll–>NFkappaB signaling pathway mediates the neuropathological effects of the human Alzheimer’s Abeta42 polypeptide in Drosophila. PLoS ONE. 2008;3(12):e3966.PubMedPubMedCentralCrossRef
186.
go back to reference Zarini-Gakiye E, Sanadgol N, Parivar K, Vaezi G. Alpha-lipoic acid ameliorates tauopathy-induced oxidative stress, apoptosis, and behavioral deficits through the balance of DIAP1/DrICE ratio and redox homeostasis: age is a determinant factor. Metab Brain Dis. 2021;36(4):669–83.PubMedCrossRef Zarini-Gakiye E, Sanadgol N, Parivar K, Vaezi G. Alpha-lipoic acid ameliorates tauopathy-induced oxidative stress, apoptosis, and behavioral deficits through the balance of DIAP1/DrICE ratio and redox homeostasis: age is a determinant factor. Metab Brain Dis. 2021;36(4):669–83.PubMedCrossRef
187.
go back to reference Cowan CM, Sealey MA, Mudher A. Suppression of tau-induced phenotypes by vitamin E demonstrates the dissociation of oxidative stress and phosphorylation in mechanisms of tau toxicity. J Neurochem. 2021;157(3):684–94.PubMedCrossRef Cowan CM, Sealey MA, Mudher A. Suppression of tau-induced phenotypes by vitamin E demonstrates the dissociation of oxidative stress and phosphorylation in mechanisms of tau toxicity. J Neurochem. 2021;157(3):684–94.PubMedCrossRef
188.
go back to reference Lohr KM, Frost B, Scherzer C, Feany MB. Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model. Proc Natl Acad Sci U S A. 2020;117(52):33608–18.PubMedPubMedCentralCrossRef Lohr KM, Frost B, Scherzer C, Feany MB. Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model. Proc Natl Acad Sci U S A. 2020;117(52):33608–18.PubMedPubMedCentralCrossRef
189.
go back to reference Siddique YH, Rahul A, Ara G, Afzal M, Varshney H, Gaur K, et al. Beneficial effects of apigenin on the transgenic Drosophila model of Alzheimer’s disease. Chem Biol Interact. 2022;366:110120.PubMedCrossRef Siddique YH, Rahul A, Ara G, Afzal M, Varshney H, Gaur K, et al. Beneficial effects of apigenin on the transgenic Drosophila model of Alzheimer’s disease. Chem Biol Interact. 2022;366:110120.PubMedCrossRef
190.
go back to reference Barati A, Masoudi R, Yousefi R, Monsefi M, Mirshafiey A. Tau and amyloid beta differentially affect the innate immune genes expression in Drosophila models of Alzheimer’s disease and β- D Mannuronic acid (M2000) modulates the dysregulation. Gene. 2022;15(808): 145972.CrossRef Barati A, Masoudi R, Yousefi R, Monsefi M, Mirshafiey A. Tau and amyloid beta differentially affect the innate immune genes expression in Drosophila models of Alzheimer’s disease and β- D Mannuronic acid (M2000) modulates the dysregulation. Gene. 2022;15(808): 145972.CrossRef
191.
go back to reference Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103(28):10793–8.PubMedPubMedCentralCrossRef Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103(28):10793–8.PubMedPubMedCentralCrossRef
192.
go back to reference Nayak N, Mishra M. Drosophila melanogaster as a model to understand the mechanisms of infection mediated neuroinflammation in neurodegenerative diseases. J Integr Neurosci. 2022;21(2):66.PubMedCrossRef Nayak N, Mishra M. Drosophila melanogaster as a model to understand the mechanisms of infection mediated neuroinflammation in neurodegenerative diseases. J Integr Neurosci. 2022;21(2):66.PubMedCrossRef
193.
go back to reference Olsen AL, Feany MB. Parkinson’s disease risk genes act in glia to control neuronal α-synuclein toxicity. Neurobiol Dis. 2021;1(159): 105482.CrossRef Olsen AL, Feany MB. Parkinson’s disease risk genes act in glia to control neuronal α-synuclein toxicity. Neurobiol Dis. 2021;1(159): 105482.CrossRef
194.
go back to reference Ranjan VD, Qiu L, Tan EK, Zeng L, Zhang Y. Modelling Alzheimer’s disease: insights from in vivo to in vitro three-dimensional culture platforms. J Tissue Eng Regen Med. 2018;12(9):1944–58.PubMedCrossRef Ranjan VD, Qiu L, Tan EK, Zeng L, Zhang Y. Modelling Alzheimer’s disease: insights from in vivo to in vitro three-dimensional culture platforms. J Tissue Eng Regen Med. 2018;12(9):1944–58.PubMedCrossRef
195.
go back to reference Doncheva NT, Palasca O, Yarani R, Litman T, Anthon C, Groenen MAM, et al. Human pathways in animal models: possibilities and limitations. Nucleic Acids Res. 2021;49(4):1859–71.PubMedPubMedCentralCrossRef Doncheva NT, Palasca O, Yarani R, Litman T, Anthon C, Groenen MAM, et al. Human pathways in animal models: possibilities and limitations. Nucleic Acids Res. 2021;49(4):1859–71.PubMedPubMedCentralCrossRef
196.
go back to reference Spangenberg EE, Lee RJ, Najafi AR, Rice RA, Elmore MRP, Blurton-Jones M, et al. Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-β pathology. Brain. 2016;139(Pt 4):1265–81.PubMedPubMedCentralCrossRef Spangenberg EE, Lee RJ, Najafi AR, Rice RA, Elmore MRP, Blurton-Jones M, et al. Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-β pathology. Brain. 2016;139(Pt 4):1265–81.PubMedPubMedCentralCrossRef
197.
go back to reference Dietrich K, Bouter Y, Müller M, Bayer TA. Synaptic alterations in mouse models for Alzheimer disease—a special focus on N-truncated abeta 4–42. Molecules. 2018;23(4):718.PubMedPubMedCentralCrossRef Dietrich K, Bouter Y, Müller M, Bayer TA. Synaptic alterations in mouse models for Alzheimer disease—a special focus on N-truncated abeta 4–42. Molecules. 2018;23(4):718.PubMedPubMedCentralCrossRef
198.
go back to reference Roda AR, Esquerda-Canals G, Martí-Clúa J, Villegas S. Cognitive impairment in the 3xTg-AD mouse model of Alzheimer’s disease is affected by Aβ-immunotherapy and cognitive stimulation. Pharmaceutics. 2020;12(10):944.PubMedPubMedCentralCrossRef Roda AR, Esquerda-Canals G, Martí-Clúa J, Villegas S. Cognitive impairment in the 3xTg-AD mouse model of Alzheimer’s disease is affected by Aβ-immunotherapy and cognitive stimulation. Pharmaceutics. 2020;12(10):944.PubMedPubMedCentralCrossRef
199.
go back to reference Li S, Jin M, Liu L, Dang Y, Ostaszewski BL, Selkoe DJ. Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer’s disease. Acta Neuropathol Commun. 2018;6(1):121.PubMedPubMedCentralCrossRef Li S, Jin M, Liu L, Dang Y, Ostaszewski BL, Selkoe DJ. Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer’s disease. Acta Neuropathol Commun. 2018;6(1):121.PubMedPubMedCentralCrossRef
200.
go back to reference Weintraub MK, Kranjac D, Eimerbrink MJ, Pearson SJ, Vinson BT, Patel J, et al. Peripheral administration of poly I: C leads to increased hippocampal amyloid-beta and cognitive deficits in a non-transgenic mouse. Behav Brain Res. 2014;266:183–7.PubMedCrossRef Weintraub MK, Kranjac D, Eimerbrink MJ, Pearson SJ, Vinson BT, Patel J, et al. Peripheral administration of poly I: C leads to increased hippocampal amyloid-beta and cognitive deficits in a non-transgenic mouse. Behav Brain Res. 2014;266:183–7.PubMedCrossRef
201.
go back to reference Loewen SM, Chavesa AM, Murray CJ, Traetta ME, Burns SE, Pekarik KH, et al. The outcomes of maternal immune activation induced with the viral mimetic poly I:C on microglia in exposed rodent offspring. Dev Neurosci. 2023;45(4):191–209.PubMedCrossRef Loewen SM, Chavesa AM, Murray CJ, Traetta ME, Burns SE, Pekarik KH, et al. The outcomes of maternal immune activation induced with the viral mimetic poly I:C on microglia in exposed rodent offspring. Dev Neurosci. 2023;45(4):191–209.PubMedCrossRef
202.
go back to reference Cheng-Hathaway PJ, Reed-Geaghan EG, Jay TR, Casali BT, Bemiller SM, Puntambekar SS, et al. The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer’s disease. Mol Neurodegener. 2018;13(1):29.PubMedPubMedCentralCrossRef Cheng-Hathaway PJ, Reed-Geaghan EG, Jay TR, Casali BT, Bemiller SM, Puntambekar SS, et al. The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer’s disease. Mol Neurodegener. 2018;13(1):29.PubMedPubMedCentralCrossRef
203.
go back to reference Zhang Y, Sloan SA, Clarke LE, Caneda C, Plaza CA, Blumenthal PD, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron. 2016;89(1):37–53.PubMedCrossRef Zhang Y, Sloan SA, Clarke LE, Caneda C, Plaza CA, Blumenthal PD, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron. 2016;89(1):37–53.PubMedCrossRef
204.
go back to reference Meeuwsen S, Bsibsi M, Persoon-Deen C, Ravid R, van Noort JM. Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus. NeuroImmunoModulation. 2005;12(4):235–45.PubMedCrossRef Meeuwsen S, Bsibsi M, Persoon-Deen C, Ravid R, van Noort JM. Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus. NeuroImmunoModulation. 2005;12(4):235–45.PubMedCrossRef
205.
go back to reference Stojkovska I, Wagner BM, Morrison BE. Parkinson’s disease and enhanced inflammatory response. Exp Biol Med. 2015;240(11):1387–95.CrossRef Stojkovska I, Wagner BM, Morrison BE. Parkinson’s disease and enhanced inflammatory response. Exp Biol Med. 2015;240(11):1387–95.CrossRef
206.
go back to reference Deng I, Corrigan F, Zhai G, Zhou XF, Bobrovskaya L. Lipopolysaccharide animal models of Parkinson’s disease: recent progress and relevance to clinical disease. Brain Behavior Immunity-Health. 2020;4: 100060.PubMedPubMedCentralCrossRef Deng I, Corrigan F, Zhai G, Zhou XF, Bobrovskaya L. Lipopolysaccharide animal models of Parkinson’s disease: recent progress and relevance to clinical disease. Brain Behavior Immunity-Health. 2020;4: 100060.PubMedPubMedCentralCrossRef
207.
208.
go back to reference Cameron T, Bennet T, Rowe EM, Anwer M, Wellington CL, Cheung KC. Review of design considerations for brain-on-a-chip models. Micromachines (Basel). 2021;12(4):441.PubMedCrossRef Cameron T, Bennet T, Rowe EM, Anwer M, Wellington CL, Cheung KC. Review of design considerations for brain-on-a-chip models. Micromachines (Basel). 2021;12(4):441.PubMedCrossRef
209.
go back to reference Cameron TC, Randhawa A, Grist SM, Bennet T, Hua J, Alde LG, et al. PDMS organ-on-chip design and fabrication: strategies for improving fluidic integration and chip robustness of rapidly prototyped microfluidic in vitro models. Micromachines (Basel). 2022;13(10):1573.PubMedCrossRef Cameron TC, Randhawa A, Grist SM, Bennet T, Hua J, Alde LG, et al. PDMS organ-on-chip design and fabrication: strategies for improving fluidic integration and chip robustness of rapidly prototyped microfluidic in vitro models. Micromachines (Basel). 2022;13(10):1573.PubMedCrossRef
210.
go back to reference Campbell SB, Wu Q, Yazbeck J, Liu C, Okhovatian S, Radisic M. Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater Sci Eng. 2020;7(7):2880–99.PubMedCrossRef Campbell SB, Wu Q, Yazbeck J, Liu C, Okhovatian S, Radisic M. Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater Sci Eng. 2020;7(7):2880–99.PubMedCrossRef
211.
go back to reference Wu Q, Liu J, Wang X, Feng L, Wu J, Zhu X, et al. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online. 2020;19:1–19.CrossRef Wu Q, Liu J, Wang X, Feng L, Wu J, Zhu X, et al. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online. 2020;19:1–19.CrossRef
212.
go back to reference Leung CM, De Haan P, Ronaldson-Bouchard K, Kim GA, Ko J, Rho HS, et al. A guide to the organ-on-a-chip. Nat Rev Methods Primers. 2022;2(1):33.CrossRef Leung CM, De Haan P, Ronaldson-Bouchard K, Kim GA, Ko J, Rho HS, et al. A guide to the organ-on-a-chip. Nat Rev Methods Primers. 2022;2(1):33.CrossRef
213.
go back to reference Piergiovanni M, Leite SB, Corvi R, Whelan M. Standardisation needs for organ on chip devices. Lab Chip. 2021;21(15):2857–68.PubMedCrossRef Piergiovanni M, Leite SB, Corvi R, Whelan M. Standardisation needs for organ on chip devices. Lab Chip. 2021;21(15):2857–68.PubMedCrossRef
214.
go back to reference Sima F, Sugioka K, Vázquez RM, Osellame R, Kelemen L, Ormos P. Three-dimensional femtosecond laser processing for lab-on-a-chip applications. Nanophotonics. 2018;7(3):613–34.CrossRef Sima F, Sugioka K, Vázquez RM, Osellame R, Kelemen L, Ormos P. Three-dimensional femtosecond laser processing for lab-on-a-chip applications. Nanophotonics. 2018;7(3):613–34.CrossRef
215.
go back to reference Paoli R, Di Giuseppe D, Badiola-Mateos M, Martinelli E, Lopez-Martinez MJ, Samitier J. Rapid manufacturing of multilayered microfluidic devices for organ on a chip applications. Sensors. 2021;21(4):1382.PubMedPubMedCentralCrossRef Paoli R, Di Giuseppe D, Badiola-Mateos M, Martinelli E, Lopez-Martinez MJ, Samitier J. Rapid manufacturing of multilayered microfluidic devices for organ on a chip applications. Sensors. 2021;21(4):1382.PubMedPubMedCentralCrossRef
216.
go back to reference Ko J, Park D, Lee S, Gumuscu B, Jeon NL. Engineering organ-on-a-chip to accelerate translational research. Micromachines (Basel). 2022;13(8):1200.PubMedCrossRef Ko J, Park D, Lee S, Gumuscu B, Jeon NL. Engineering organ-on-a-chip to accelerate translational research. Micromachines (Basel). 2022;13(8):1200.PubMedCrossRef
217.
go back to reference Puryear JR III, Yoon JK, Kim Y. Advanced fabrication techniques of microengineered physiological systems. Micromachines (Basel). 2020;11(8):730.CrossRef Puryear JR III, Yoon JK, Kim Y. Advanced fabrication techniques of microengineered physiological systems. Micromachines (Basel). 2020;11(8):730.CrossRef
218.
go back to reference Kim J, Yoon T, Kim P, Bekhbat M, Kang SM, Rho HS, et al. Manufactured tissue-to-tissue barrier chip for modeling the human blood–brain barrier and regulation of cellular trafficking. Lab Chip. 2023;23:2990–3001.PubMedCrossRef Kim J, Yoon T, Kim P, Bekhbat M, Kang SM, Rho HS, et al. Manufactured tissue-to-tissue barrier chip for modeling the human blood–brain barrier and regulation of cellular trafficking. Lab Chip. 2023;23:2990–3001.PubMedCrossRef
219.
go back to reference Convery N, Samardzhieva I, Stormonth-Darling JM, Harrison S, Sullivan GJ, Gadegaard N. 3D printed tooling for injection molded microfluidics. Macromol Mater Eng. 2021;306(11):2100464.CrossRef Convery N, Samardzhieva I, Stormonth-Darling JM, Harrison S, Sullivan GJ, Gadegaard N. 3D printed tooling for injection molded microfluidics. Macromol Mater Eng. 2021;306(11):2100464.CrossRef
220.
go back to reference Kane KIW, Jarazo J, Moreno EL, Fleming RMT, Schwamborn JC. Passive controlled flow for Parkinson’s disease neuronal cell culture in 3D microfluidic devices. Organs-on-a-Chip. 2020;2: 100005.CrossRef Kane KIW, Jarazo J, Moreno EL, Fleming RMT, Schwamborn JC. Passive controlled flow for Parkinson’s disease neuronal cell culture in 3D microfluidic devices. Organs-on-a-Chip. 2020;2: 100005.CrossRef
221.
go back to reference Zhou Y, Qiao H, Xu F, Zhao W, Wang J, Gu L, et al. Bioengineering of a human physiologically relevant microfluidic blood–cerebrospinal fluid barrier model. Lab Chip. 2023;23:3002–15.PubMedCrossRef Zhou Y, Qiao H, Xu F, Zhao W, Wang J, Gu L, et al. Bioengineering of a human physiologically relevant microfluidic blood–cerebrospinal fluid barrier model. Lab Chip. 2023;23:3002–15.PubMedCrossRef
222.
go back to reference Brown JA, Codreanu SG, Shi M, Sherrod SD, Markov DA, Neely MD, et al. Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit. J Neuroinflammation. 2016;13(1):1–17.CrossRef Brown JA, Codreanu SG, Shi M, Sherrod SD, Markov DA, Neely MD, et al. Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit. J Neuroinflammation. 2016;13(1):1–17.CrossRef
223.
go back to reference Salmon I, Grebenyuk S, Fattah ARA, Rustandi G, Pilkington T, Verfaillie C, et al. Engineering neurovascular organoids with 3D printed microfluidic chips. Lab Chip. 2022;22(8):1615–29.PubMedCrossRef Salmon I, Grebenyuk S, Fattah ARA, Rustandi G, Pilkington T, Verfaillie C, et al. Engineering neurovascular organoids with 3D printed microfluidic chips. Lab Chip. 2022;22(8):1615–29.PubMedCrossRef
224.
go back to reference Kang YJ, Diep YN, Tran M, Tran VTA, Ambrin G, Ngo H, et al. Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration. Nat Protocols. 2023;18(9):2838–67.PubMedCrossRef Kang YJ, Diep YN, Tran M, Tran VTA, Ambrin G, Ngo H, et al. Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration. Nat Protocols. 2023;18(9):2838–67.PubMedCrossRef
225.
go back to reference Park J, Wetzel I, Marriott I, Dréau D, D’Avanzo C, Kim DY, et al. A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nat Neurosci. 2018;21(7):941–51.PubMedPubMedCentralCrossRef Park J, Wetzel I, Marriott I, Dréau D, D’Avanzo C, Kim DY, et al. A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nat Neurosci. 2018;21(7):941–51.PubMedPubMedCentralCrossRef
226.
go back to reference Park J, Baik SH, Mook-Jung I, Irimia D, Cho H. Mimicry of central-peripheral immunity in Alzheimer’s disease and discovery of neurodegenerative roles in neutrophil. Front Immunol. 2019;10:480449.CrossRef Park J, Baik SH, Mook-Jung I, Irimia D, Cho H. Mimicry of central-peripheral immunity in Alzheimer’s disease and discovery of neurodegenerative roles in neutrophil. Front Immunol. 2019;10:480449.CrossRef
227.
go back to reference Seo S, Choi CH, Yi KS, Kim SU, Lee K, Choi N, et al. An engineered neurovascular unit for modeling neuroinflammation. Biofabrication. 2021;13(3): 035039.CrossRef Seo S, Choi CH, Yi KS, Kim SU, Lee K, Choi N, et al. An engineered neurovascular unit for modeling neuroinflammation. Biofabrication. 2021;13(3): 035039.CrossRef
228.
go back to reference Seo S, Jang M, Kim H, Sung JH, Choi N, Lee K, et al. Neuro-glia-vascular-on-a-chip system to assess aggravated neurodegeneration via brain endothelial cells upon exposure to diesel exhaust particles. Adv Funct Mater. 2023;33(12):2210123.CrossRef Seo S, Jang M, Kim H, Sung JH, Choi N, Lee K, et al. Neuro-glia-vascular-on-a-chip system to assess aggravated neurodegeneration via brain endothelial cells upon exposure to diesel exhaust particles. Adv Funct Mater. 2023;33(12):2210123.CrossRef
229.
go back to reference Jorfi M, D’Avanzo C, Kim DY, Irimia D. Three-dimensional models of the human brain development and diseases. Adv Healthc Mater. 2018;7(1). Jorfi M, D’Avanzo C, Kim DY, Irimia D. Three-dimensional models of the human brain development and diseases. Adv Healthc Mater. 2018;7(1).
230.
231.
go back to reference Fernandes JTS, Chutna O, Chu V, Conde JP, Outeiro TF. A novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson’s disease and other synucleinopathies. Front Neurosci. 2016;10:227609.CrossRef Fernandes JTS, Chutna O, Chu V, Conde JP, Outeiro TF. A novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson’s disease and other synucleinopathies. Front Neurosci. 2016;10:227609.CrossRef
232.
go back to reference de Rus JA, Alpaugh M, Denis HL, Tancredi JL, Boutin M, Decaestecker J, et al. The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson’s disease. Nat Commun. 2023;14(1):3651.CrossRef de Rus JA, Alpaugh M, Denis HL, Tancredi JL, Boutin M, Decaestecker J, et al. The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson’s disease. Nat Commun. 2023;14(1):3651.CrossRef
233.
go back to reference Pediaditakis I, Kodella KR, Manatakis DV, Hinojosa CD, Manolakos ES, Rubin LL, et al. Modeling Alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption in Parkinson’s disease. BioRxiv. 2021;2020–7. Pediaditakis I, Kodella KR, Manatakis DV, Hinojosa CD, Manolakos ES, Rubin LL, et al. Modeling Alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption in Parkinson’s disease. BioRxiv. 2021;2020–7.
Metadata
Title
Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases
Authors
Wendy Balestri
Ruchi Sharma
Victor A. da Silva
Bianca C. Bobotis
Annabel J. Curle
Vandana Kothakota
Farnoosh Kalantarnia
Maria V. Hangad
Mina Hoorfar
Joanne L. Jones
Marie-Ève Tremblay
Jehan J. El-Jawhari
Stephanie M. Willerth
Yvonne Reinwald
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-024-03024-8

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