Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2023

Open Access 01-12-2023 | Research

Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis

Authors: Yuriy Pomeshchik, Erika Velasquez, Jeovanis Gil, Oxana Klementieva, Ritha Gidlöf, Marie Sydoff, Silvia Bagnoli, Benedetta Nacmias, Sandro Sorbi, Gunilla Westergren-Thorsson, Gunnar K. Gouras, Melinda Rezeli, Laurent Roybon

Published in: Acta Neuropathologica Communications | Issue 1/2023

Login to get access

Abstract

The hippocampus is a primary region affected in Alzheimer’s disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis by comparing patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of pathways and network dysfunction in AD patient brain cells, associated with increased levels of Aβ-42 and β-sheet structures. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of early to end stage AD cellular pathogenesis. Our data showcase patient-based models to study the cell autonomous origin and progression of AD pathogenesis.

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
2.
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140PubMedPubMedCentralCrossRef
3.
Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221PubMedCrossRef
4.
Sasaguri H, Hashimoto S, Watamura N, Sato K, Takamura R, Nagata K, Tsubuki S, Ohshima T, Yoshiki A, Sato K, Kumita W, Sasaki E, Kitazume S, Nilsson P, Winblad B, Saito T, Iwata N, Saido TC (2022) Recent advances in the modeling of Alzheimer’s disease. Front Neurosci 16:807473PubMedPubMedCentralCrossRef
5.
Konttinen H, Cabral-da-Silva MEC, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, Giugno R, Ishchenko Y, Hernandez D, Fazaludeen MF, Eamen S, Budia MG, Fagerlund I, Scoyni F, Korhonen P, Huber N, Haapasalo A, Hewitt AW, Vickers J, Smith GC, Oksanen M, Graff C, Kanninen KM, Lehtonen S, Propson N, Schwartz MP, Pebay A, Koistinaho J, Ooi L, Malm T (2019) PSEN1DeltaE9, APPswe, and APOE4 confer disparate phenotypes in human iPSC-derived microglia. Stem Cell Reports 13(4):669–683PubMedPubMedCentralCrossRef
6.
Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno S, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12(4):487–496PubMedCrossRef
7.
Pomeshchik Y, Klementieva O, Gil J, Martinsson I, Hansen MG, de Vries T, Sancho-Balsells A, Russ K, Savchenko E, Collin A, Vaz AR, Bagnoli S, Nacmias B, Rampon C, Sorbi S, Brites D, Marko-Varga G, Kokaia Z, Rezeli M, Gouras GK, Roybon L (2020) Human iPSC-derived hippocampal spheroids: an innovative tool for stratifying alzheimer disease patient-specific cellular phenotypes and developing therapies. Stem Cell Reports 15(1):256–273PubMedPubMedCentralCrossRef
8.
Penney J, Ralvenius WT, Tsai LH (2020) Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol Psychiatry 25(1):148–167PubMedCrossRef
9.
Verheijen MCT, Krauskopf J, Caiment F, Nazaruk M, Wen QF, van Herwijnen MHM, Hauser DA, Gajjar M, Verfaillie C, Vermeiren Y, De Deyn PP, Wittens MMJ, Sieben A, Engelborghs S, Dejonckheere W, Princen K, Griffioen G, Roggen EL, Briede JJ (2022) iPSC-derived cortical neurons to study sporadic Alzheimer disease: a transcriptome comparison with post-mortem brain samples. Toxicol Lett 356:89–99PubMedCrossRef
10.
Zhao J, Fu Y, Yamazaki Y, Ren Y, Davis MD, Liu CC, Lu W, Wang X, Chen K, Cherukuri Y, Jia L, Martens YA, Job L, Shue F, Nguyen TT, Younkin SG, Graff-Radford NR, Wszolek ZK, Brafman DA, Asmann YW, Ertekin-Taner N, Kanekiyo T, Bu G (2020) APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids. Nat Commun 11(1):5540PubMedPubMedCentralCrossRef
11.
Kwart D, Gregg A, Scheckel C, Murphy EA, Paquet D, Duffield M, Tessier-Lavigne M (2019) A large panel of isogenic APP and PSEN1 mutant human iPSC neurons reveals shared endosomal abnormalities mediated by APP β-CTFs, not Aβ. Neuron 104(2):256–270PubMedCrossRef
12.
Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T, Benjamin LN, Walsh DM, Selkoe DJ, Young-Pearse TL (2014) The familial Alzheimer’s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum Mol Genet 23(13):3523–3536PubMedPubMedCentralCrossRef
13.
Sproul AA, Jacob S, Pre D, Kim SH, Nestor MW, Navarro-Sobrino M, Santa-Maria I, Zimmer M, Aubry S, Steele JW, Kahler DJ, Dranovsky A, Arancio O, Crary JF, Gandy S, Noggle SA (2014) Characterization and molecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neural progenitors. PLoS ONE 9(1):e84547PubMedPubMedCentralCrossRef
14.
Windrem MS, Osipovitch M, Liu Z, Bates J, Chandler-Militello D, Zou L, Goldman SA (2017) Human iPSC glial mouse chimeras reveal glial contributions to schizophrenia. Cell Stem Cell 21(2):195–208PubMedPubMedCentralCrossRef
15.
Osipovitch M, Martinez AA, Mariani JN, Cornwell A, Dhaliwal S, Zou L, Goldman SA (2019) Human ESC-derived chimeric mouse models of Huntington’s disease reveal cell-intrinsic defects in glial progenitor cell differentiation. Cell Stem Cell 24(1):107–122PubMedCrossRef
16.
Najm R, Zalocusky KA, Zilberter M, Yoon SY, Hao Y, Koutsodendris N, Nelson M, Rao A, Taubes A, Jones EA, Huang Y (2020) In vivo chimeric Alzheimer’s disease modeling of apolipoprotein E4 toxicity in human neurons. Cell Rep 32(4):107962PubMedPubMedCentralCrossRef
17.
Espuny-Camacho I, Arranz AM, Fiers M, Snellinx A, Ando K, Munck S, De Strooper B (2017) Hallmarks of Alzheimer’s disease in stem-cell-derived human neurons transplanted into mouse brain. Neuron 93(5):1066–1081PubMedCrossRef
18.
Preman P, Tcw J, Calafate S, Snellinx A, Alfonso-Triguero M, Corthout N, Munck S, Thal DR, Goate AM, De Strooper B, Arranz AM (2021) Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques. Mol Neurodegener 16(1):68PubMedPubMedCentralCrossRef
19.
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239–259PubMedCrossRef
20.
Matsuda H, Ito K, Ishii K, Shimosegawa E, Okazawa H, Mishina M, Mizumura S, Ishii K, Okita K, Shigemoto Y, Kato T, Takenaka A, Kaida H, Hanaoka K, Matsunaga K, Hatazawa J, Ikawa M, Tsujikawa T, Morooka M, Ishibashi K, Kameyama M, Yamao T, Miwa K, Ogawa M, Sato N (2020) Quantitative evaluation of (18)F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study. Front Neurol 11:578753PubMedCrossRef
21.
Bouter C, Bouter Y (2019) (18)F-FDG-PET in mouse models of Alzheimer’s disease. Front Med (Lausanne) 6:71PubMedCrossRef
22.
Klementieva O, Willen K, Martinsson I, Israelsson B, Engdahl A, Cladera J, Uvdal P, Gouras GK (2017) Pre-plaque conformational changes in Alzheimer’s disease-linked Abeta and APP. Nat Commun 8:14726PubMedPubMedCentralCrossRef
23.
Wu M, Zhang M, Yin X, Chen K, Hu Z, Zhou Q, Cao X, Chen Z, Liu D (2021) The role of pathological tau in synaptic dysfunction in Alzheimer’s diseases. Transl Neurodegener 10(1):45PubMedPubMedCentralCrossRef
24.
Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG (2007) Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener 2:18PubMedPubMedCentralCrossRef
25.
Delacourte A (1990) General and dramatic glial reaction in Alzheimer brains. Neurology 40(1):33–37PubMedCrossRef
26.
Reichenbach N, Delekate A, Plescher M, Schmitt F, Krauss S, Blank N, Petzold GC (2019) Inhibition of Stat3-mediated astrogliosis ameliorates pathology in an Alzheimer’s disease model. EMBO Mol Med 11(2):e9665PubMedPubMedCentralCrossRef
27.
Toral-Rios D, Patiño-López G, Gómez-Lira G, Gutiérrez R, Becerril-Pérez F, Rosales-Córdova A, Campos-Peña V (2020) Activation of STAT3 regulates reactive astrogliosis and neuronal death induced by AβO neurotoxicity. Int J Mol Sci 21(20):7458PubMedPubMedCentralCrossRef
28.
29.
Tam SY, Lilla JN, Chen CC, Kalesnikoff J, Tsai M (2015) RabGEF1/Rabex-5 regulates TrkA-mediated neurite outgrowth and nmda-induced signaling activation in NGF-differentiated PC12 cells. PLoS ONE 10(11):e0142935PubMedPubMedCentralCrossRef
30.
31.
Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Zhang B (2021) Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Sci Adv 7(2):eabb5398PubMedPubMedCentralCrossRef
32.
Okano H, Morimoto S (2022) iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell Stem Cell 29(2):189–208PubMedCrossRef
33.
Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, Jain BR, Bertelsen SE, Kapoor M, Marcora E, Sikora E, Andrews EJ, Martini AC, Karch CM, Head E, Holtzman DM, Zhang B, Wang M, Maxfield FR, Poon WW, Goate AM (2022) Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell 185(13):2213–2233PubMedPubMedCentralCrossRef
34.
Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Olivé MG, Koistinaho J (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer’s disease. Stem Cell Reports 9(6):1885–1897PubMedPubMedCentralCrossRef
35.
Shimada H, Sato Y, Sasaki T, Shimozawa A, Imaizumi K, Shindo T, Miyao S, Kiyama K, Kondo T, Shibata S, Ishii S, Kuromitsu J, Aoyagi H, Ito D, Okano H (2022) A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer. Cell Rep Methods 2(9):100289PubMedPubMedCentralCrossRef
36.
Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, De Luca GC, Crary JF, Casaccia P, Buxbaum JD, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B (2016) Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease. Genome Med 8(1):104PubMedPubMedCentralCrossRef
37.
Wang M, Beckmann ND, Roussos P, Wang E, Zhou X, Wang Q, Ming C, Neff R, Ma W, Fullard JF, Hauberg ME, Bendl J, Peters MA, Logsdon B, Wang P, Mahajan M, Mangravite LM, Dammer EB, Duong DM, Lah JJ, Seyfried NT, Levey AI, Buxbaum JD, Ehrlich M, Gandy S, Katsel P, Haroutunian V, Schadt E, Zhang B (2018) The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer’s disease. Sci Data 5:180185PubMedPubMedCentralCrossRef
38.
39.
Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van Den Haute C, Mercken M, Moechars D, Laenen I, Kuiperi C, Bruynseels K, Tesseur I, Loos R, Vanderstichele H, Checler F, Sciot R, Van Leuven F (2000) Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the london mutant of human APP in neurons. Am J Pathol 157(4):1283–1298PubMedPubMedCentralCrossRef
40.
Albert K, Niskanen J, Kälvälä S, Lehtonen Š (2021) Utilising induced pluripotent stem cells in neurodegenerative disease research: focus on glia. Int J Mol Sci 22(9):4334PubMedPubMedCentralCrossRef
41.
42.
Habib N, McCabe C, Medina S, Varshavsky M, Kitsberg D, Dvir-Szternfeld R, Green G, Dionne D, Nguyen L, Marshall JL, Chen F, Zhang F, Kaplan T, Regev A, Schwartz M (2020) Disease-associated astrocytes in Alzheimer’s disease and aging. Nat Neurosci 23(6):701–706PubMedPubMedCentralCrossRef
43.
Salcedo C, Andersen JV, Vinten KT, Pinborg LH, Waagepetersen HS, Freude KK, Aldana BI (2021) Functional metabolic mapping reveals highly active branched-chain amino acid metabolism in human astrocytes. Which Is Impaired in iPSC-Derived Astrocytes in Alzheimer’s Disease, Front Aging Neurosci 13:736580PubMed
44.
Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, Menon M, He L, Abdurrob F, Jiang X, Martorell AJ, Ransohoff RM, Hafler BP, Bennett DA, Kellis M, Tsai LH (2019) Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570(7761):332–337PubMedPubMedCentralCrossRef
45.
Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, Pflueger J, Lister R, Rackham OJL, Petretto E, Polo JM (2019) A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat Neurosci 22(12):2087–2097PubMedCrossRef
46.
Smith AM, Davey K, Tsartsalis S, Khozoie C, Fancy N, Tang SS, Liaptsi E, Weinert M, McGarry A, Muirhead RCJ, Gentleman S, Owen DR, Matthews PM (2022) Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology. Acta Neuropathol 143(1):75–91PubMedCrossRef
47.
Russ K, Teku G, Bousset L, Redeker V, Piel S, Savchenko E, Pomeshchik Y, Savistchenko J, Stummann TC, Azevedo C, Collin A, Goldwurm S, Fog K, Elmer E, Vihinen M, Melki R, Roybon L (2021) TNF-alpha and alpha-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration. Cell Rep 34(12):108895PubMedCrossRef
48.
Wang W, Zhao F, Ma X, Perry G, Zhu X (2020) Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener 15(1):30PubMedPubMedCentralCrossRef
49.
50.
Kobro-Flatmoen A, Lagartos-Donate MJ, Aman Y, Edison P, Witter MP, Fang EF (2021) Re-emphasizing early Alzheimer’s disease pathology starting in select entorhinal neurons, with a special focus on mitophagy. Ageing Res Rev 67:101307PubMedCrossRef
51.
52.
53.
54.
Chudobova J, Zempel H (2023) Microtubule affinity regulating kinase (MARK/Par1) isoforms differentially regulate Alzheimer-like TAU missorting and Abeta-mediated synapse pathology. Neural Regen Res 18(2):335–336PubMedCrossRef
55.
Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM (2017) Synaptic impairment in Alzheimer’s disease: a dysregulated symphony. Trends Neurosci 40(6):347–357PubMedCrossRef
56.
Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27(10):1372–1384PubMedCrossRef
57.
Aoyagi A, Condello C, Stöhr J, Yue W, Rivera BM, Lee JC, Prusiner SB (2019) Aβ and tau prion-like activities decline with longevity in the Alzheimer’s disease human brain. Sci Trans Med 11(490):eaat8462CrossRef
58.
Gomez-Gutierrez R, Morales R (2020) The prion-like phenomenon in Alzheimer’s disease: evidence of pathology transmission in humans. PLoS Pathog 16(10):e1009004PubMedPubMedCentralCrossRef
59.
Hu NW, Corbett GT, Moore S, Klyubin I, O’Malley TT, Walsh DM, Livesey FJ, Rowan MJ (2018) Extracellular forms of abeta and tau from iPSC models of Alzheimer’s disease disrupt synaptic plasticity. Cell Rep 23(7):1932–1938PubMedPubMedCentralCrossRef
60.
Ayers JI, Giasson BI, Borchelt DR (2018) Prion-like spreading in tauopathies. Biol Psychiatry 83(4):337–346PubMedCrossRef
61.
Condello C, Stoehr J (2018) Abeta propagation and strains: Implications for the phenotypic diversity in Alzheimer’s disease. Neurobiol Dis 109(Pt B):191–200PubMedCrossRef
62.
Roos TT, Garcia MG, Martinsson I, Mabrouk R, Israelsson B, Deierborg T, Kobro-Flatmoen A, Tanila H, Gouras GK (2021) Neuronal spreading and plaque induction of intracellular Abeta and its disruption of Abeta homeostasis. Acta Neuropathol 142(4):669–687PubMedPubMedCentralCrossRef
63.
Sleegers K, Brouwers N, Gijselinck I, Theuns J, Goossens D, Wauters J, Del-Favero J, Cruts M, van Duijn CM, Van Broeckhoven C (2006) APP duplication is sufficient to cause early onset Alzheimer’s dementia with cerebral amyloid angiopathy. Brain 129(Pt 11):2977–2983PubMedCrossRef
64.
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M (2021) Alzheimer’s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol 20(11):930–942PubMedPubMedCentralCrossRef
65.
Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38(1):24–26PubMedCrossRef
66.
Davis-Salinas J, Van Nostrand WE (1995) Amyloid beta-protein aggregation nullifies its pathologic properties in cultured cerebrovascular smooth muscle cells. J Biol Chem 270(36):20887–20890PubMedCrossRef
67.
Saura CA, Deprada A, Capilla-Lopez MD, Parra-Damas A (2023) Revealing cell vulnerability in Alzheimer’s disease by single-cell transcriptomics. Semin Cell Dev Biol 139:73–83PubMedCrossRef
68.
Blanchard JW, Akay LA, Davila-Velderrain J, von Maydell D, Mathys H, Davidson SM, Effenberger A, Chen CY, Maner-Smith K, Hajjar I, Ortlund EA, Bula M, Agbas E, Ng A, Jiang X, Kahn M, Blanco-Duque C, Lavoie N, Liu L, Reyes R, Lin YT, Ko T, R’Bibo L, Ralvenius WT, Bennett DA, Cam HP, Kellis M, Tsai LH (2022) APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature 611(7937):769–779PubMedPubMedCentralCrossRef
69.
Nasrabady SE, Rizvi B, Goldman JE, Brickman AM (2018) White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun 6(1):22PubMedPubMedCentralCrossRef
70.
Azevedo C, Teku G, Pomeshchik Y, Reyes JF, Chumarina M, Russ K, Savchenko E, Hammarberg A, Lamas NJ, Collin A, Gouras GK, Klementieva O, Hallbeck M, Taipa R, Vihinen M, Roybon L (2022) Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein-induced changes in maturation and immune reactive properties. Proc Natl Acad Sci U S A 119(12):e2111405119PubMedPubMedCentralCrossRef
71.
Venegas C, Kumar S, Franklin BS, Dierkes T, Brinkschulte R, Tejera D, Vieira-Saecker A, Schwartz S, Santarelli F, Kummer MP, Griep A, Gelpi E, Beilharz M, Riedel D, Golenbock DT, Geyer M, Walter J, Latz E, Heneka MT (2017) Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature 552(7685):355–361PubMedCrossRef
72.
73.
Fagerlund I, Dougalis A, Shakirzyanova A, Gómez-Budia M, Pelkonen A, Konttinen H, Malm T (2021) Microglia-like cells promote neuronal functions in cerebral organoids. Cells 11(1):124PubMedPubMedCentralCrossRef
74.
Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, Johnston S, Parylak SL, Jin X, Gage FH (2018) An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36(5):432–441PubMedPubMedCentralCrossRef
75.
Revah O, Gore F, Kelley KW, Andersen J, Sakai N, Chen X, Li MY, Birey F, Yang X, Saw NL, Baker SW, Amin ND, Kulkarni S, Mudipalli R, Cui B, Nishino S, Grant GA, Knowles JK, Shamloo M, Huguenard JR, Deisseroth K, Pasca SP (2022) Maturation and circuit integration of transplanted human cortical organoids. Nature 610(7931):319–326PubMedPubMedCentralCrossRef
76.
Chumarina M, Russ K, Azevedo C, Heuer A, Pihl M, Collin A, Roybon L (2019) Cellular alterations identified in pluripotent stem cell-derived midbrain spheroids generated from a female patient with progressive external ophthalmoplegia and parkinsonism who carries a novel variation (p. Q811R) in the POLG1 gene. Acta Neuropathol Commun 7:1–19CrossRef
77.
Lagomarsino VN, Pearse RV 2nd, Liu L, Hsieh YC, Fernandez MA, Vinton EA, Paull D, Felsky D, Tasaki S, Gaiteri C, Vardarajan B, Lee H, Muratore CR, Benoit CR, Chou V, Fancher SB, He A, Merchant JP, Duong DM, Martinez H, Zhou M, Bah F, Vicent MA, Stricker JMS, Xu J, Dammer EB, Levey AI, Chibnik LB, Menon V, Seyfried NT, De Jager PL, Noggle S, Selkoe DJ, Bennett DA, Young-Pearse TL (2021) Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors. Neuron 109(21):3402–3420PubMedPubMedCentralCrossRef
78.
79.
80.
Donnelly KM, Coleman CM, Fuller ML, Reed VL, Smerina D, Tomlinson DS, Pearce MMP (2022) Hunting for the cause: evidence for prion-like mechanisms in Huntington’s disease. Front Neurosci 16:946822PubMedPubMedCentralCrossRef
81.
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HU, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B (2021) Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits. Key Regulators, Potential Therapeutics Alzheimer’s Disease, Neuron 109(2):257–272PubMed
82.
Mirhadi S, Tam S, Li Q, Moghal N, Pham NA, Tong J, Golbourn BJ, Krieger JR, Taylor P, Li M, Weiss J, Martins-Filho SN, Raghavan V, Mamatjan Y, Khan AA, Cabanero M, Sakashita S, Huo K, Agnihotri S, Ishizawa K, Waddell TK, Zadeh G, Yasufuku K, Liu G, Shepherd FA, Moran MF, Tsao MS (2022) Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes. Nat Commun 13(1):1811PubMedPubMedCentralCrossRef
83.
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10(1):1523PubMedPubMedCentralCrossRef
84.
Mair P, Wilcox R (2020) Robust statistical methods in R using the WRS2 package. Behav Res Methods 52(2):464–488PubMedCrossRef
Metadata
Title
Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Authors
Yuriy Pomeshchik
Erika Velasquez
Jeovanis Gil
Oxana Klementieva
Ritha Gidlöf
Marie Sydoff
Silvia Bagnoli
Benedetta Nacmias
Sandro Sorbi
Gunilla Westergren-Thorsson
Gunnar K. Gouras
Melinda Rezeli
Laurent Roybon
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2023
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-023-01649-z

Other articles of this Issue 1/2023

Acta Neuropathologica Communications 1/2023 Go to the issue

Research

Deep histopathology genotype–phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb

Case report

Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature

Research

Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy

Research

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

Research

Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology

Research

NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment