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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Alzheimer's Disease | Research

Glial activation and inflammation along the Alzheimer’s disease continuum

Authors: Kaja Nordengen, Bjørn-Eivind Kirsebom, Kristi Henjum, Per Selnes, Berglind Gísladóttir, Marianne Wettergreen, Silje Bøen Torsetnes, Gøril Rolfseng Grøntvedt, Knut K. Waterloo, Dag Aarsland, Lars N. G. Nilsson, Tormod Fladby

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Background

Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer’s disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation.

Methods

We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker—soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction—monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers—chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker—fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn’s pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score.

Results

Compared to healthy controls, sTREM2 was increased in SCD (p < .01), MCI (p < .05), and AD dementia cases (p < .001) and increased in AD dementia compared to MCI cases (p < .05). MCP-1 was increased in MCI (p < .05) and AD dementia compared to both healthy controls (p < .001) and SCD cases (p < .01). YKL-40 was increased in dementia compared to healthy controls (p < .01) and MCI (p < .05). All of the CSF activation markers were increased in subjects with pathological CSF T-tau (A+T−N+ and A+T+N+), compared to subjects without neurodegeneration (A−T−N− and A+T−N−).

Discussion

Microglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aβ+ cases (A+) with pathological T-tau (N+). Possible different effects of early and later glial activation need to be explored.
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Literature
1.
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535–62.PubMedPubMedCentralCrossRef
2.
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87(5):539–47.PubMedPubMedCentralCrossRef
3.
Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chetelat G, et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2014;10(6):844–52.CrossRef
4.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2011;7(3):270–9.CrossRef
5.
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia : the journal of the Alzheimer's Association. 2011;7(3):280–92.CrossRef
6.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2011;7(3):263–9.CrossRef
7.
Fladby T, Palhaugen L, Selnes P, Waterloo K, Brathen G, Hessen E, et al. Detecting at-risk Alzheimer's disease cases. J Alzheimers Dis. 2017;60(1):97–105.PubMedPubMedCentralCrossRef
8.
Reijs BL, Teunissen CE, Goncharenko N, Betsou F, Blennow K, Baldeiras I, et al. The central biobank and virtual biobank of BIOMARKAPD: a resource for studies on neurodegenerative diseases. Front Neurol. 2015;6:216.PubMedPubMedCentralCrossRef
9.
Villegas-Llerena C, Phillips A, Garcia-Reitboeck P, Hardy J, Pocock JM. Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease. Curr Opin Neurobiol. 2016;36:74–81.PubMedCrossRef
10.
Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med. 2013;368(2):107–16.PubMedCrossRef
11.
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
12.
Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, et al. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron. 2005;48(6):913–22.PubMedCrossRef
13.
Mandrekar S, Jiang Q, Lee CY, Koenigsknecht-Talboo J, Holtzman DM, Landreth GE. Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis. J Neurosci. 2009;29(13):4252–62.PubMedPubMedCentralCrossRef
14.
Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457–70.PubMedPubMedCentralCrossRef
15.
Neniskyte U, Gross CT. Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders. Nat Rev Neurosci. 2017;18(11):658–70.PubMedCrossRef
16.
17.
Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013;368(2):117–27.PubMedCrossRef
18.
International Genomics of Alzheimer’s Disease Consortium (IGAP). Convergent genetic and expression data implicate immunity in Alzheimer's disease. Alzheimers Dement. 2015;11(6):658–71.CrossRef
19.
Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23(6):512–33.PubMedCrossRef
20.
21.
22.
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14(4):388–405.PubMedPubMedCentralCrossRef
23.
Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci. 2008;28(33):8354–60.PubMedPubMedCentralCrossRef
24.
Patterson BW, Elbert DL, Mawuenyega KG, Kasten T, Ovod V, Ma S, et al. Age and amyloid effects on human central nervous system amyloid-beta kinetics. Ann Neurol. 2015;78(3):439–53.PubMedPubMedCentralCrossRef
25.
Hamelin L, Lagarde J, Dorothee G, Leroy C, Labit M, Comley RA, et al. Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016;139(Pt 4):1252–64.PubMedCrossRef
26.
Fan Z, Brooks DJ, Okello A. Edison P. Brain: An early and late peak in microglial activation in Alzheimer's disease trajectory; 2017.
27.
Brendel M, Kleinberger G, Probst F, Jaworska A, Overhoff F, Blume T, et al. Increase of TREM2 during aging of an Alzheimer's disease mouse model is paralleled by microglial activation and amyloidosis. Front Aging Neurosci. 2017;9:8.PubMedPubMedCentralCrossRef
28.
Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J Exp Med. 2016;213(5):667–75.PubMedPubMedCentralCrossRef
29.
Suarez-Calvet M, Kleinberger G, Araque Caballero MA, Brendel M, Rominger A, Alcolea D, et al. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers. EMBO Mol Med. 2016;8(5):466–76.PubMedPubMedCentralCrossRef
30.
Gispert JD, Suarez-Calvet M, Monte GC, Tucholka A, Falcon C, Rojas S, et al. Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer's disease. Alzheimers Dement. 2016;12(12):1259–72.PubMedCrossRef
31.
Atagi Y, Liu CC, Painter MM, Chen XF, Verbeeck C, Zheng H, et al. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J Biol Chem. 2015;290(43):26043–50.PubMedPubMedCentralCrossRef
32.
33.
Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-Beta by microglia. Neuron. 2016;91(2):328–40.PubMedCrossRef
34.
Pasinetti GM, Johnson SA, Oda T, Rozovsky I, Finch CE. Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain. J Comp Neurol. 1994;339(3):387–400.PubMedCrossRef
35.
Li X, Ma Y, Wei X, Li Y, Wu H, Zhuang J, et al. Clusterin in Alzheimer's disease: a player in the biological behavior of amyloid-beta. Neurosci Bull. 2014;30(1):162–8.PubMedCrossRef
36.
Yu JT, Tan L. The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy. Mol Neurobiol. 2012;45(2):314–26.PubMedCrossRef
37.
Deming Y, Xia J, Cai Y, Lord J, Holmans P, Bertelsen S, et al. A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin. Neurobiol Aging. 2016;37:208.e1–.e9.
38.
Gispert JD, Monte GC, Falcon C, Tucholka A, Rojas S, Sanchez-Valle R, et al. CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD. Neurobiol Aging. 2016;38:47–55.PubMedCrossRef
39.
Llorens F, Thune K, Tahir W, Kanata E, Diaz-Lucena D, Xanthopoulos K, et al. YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias. Mol Neurodegener. 2017;12(1):83.PubMedPubMedCentralCrossRef
40.
Antonell A, Mansilla A, Rami L, Llado A, Iranzo A, Olives J, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer's disease. J Alzheimers Dis. 2014;42(3):901–8.PubMedCrossRef
41.
Chen P, Zhao W, Guo Y, Xu J, Yin M. CX3CL1/CX3CR1 in Alzheimer's disease: a target for neuroprotection. Biomed Res Int. 2016;2016:8090918.PubMedPubMedCentral
42.
Zujovic V, Benavides J, Vige X, Carter C, Taupin V. Fractalkine modulates TNF-alpha secretion and neurotoxicity induced by microglial activation. Glia. 2000;29(4):305–15.PubMedCrossRef
43.
Mizuno T, Kawanokuchi J, Numata K, Suzumura A. Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res. 2003;979(1–2):65–70.PubMedCrossRef
44.
Pabon MM, Bachstetter AD, Hudson CE, Gemma C, Bickford PC. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease. J Neuroinflammation. 2011;8:9.PubMedPubMedCentralCrossRef
45.
Strobel S, Grunblatt E, Riederer P, Heinsen H, Arzberger T, Al-Sarraj S, et al. Changes in the expression of genes related to neuroinflammation over the course of sporadic Alzheimer's disease progression: CX3CL1, TREM2, and PPARgamma. J Neural Transm. 2015;122(7):1069–76.PubMedCrossRef
46.
Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interf Cytokine Res. 2009;29(6):313–26.CrossRef
47.
Perea JR, Lleo A, Alcolea D, Fortea J, Avila J, Bolos M. Decreased CX3CL1 levels in the cerebrospinal fluid of patients with Alzheimer's disease. Front Neurosci. 2018;12:609.PubMedPubMedCentralCrossRef
48.
Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H, et al. The role of clusterin in amyloid-beta-associated neurodegeneration. JAMA Neurol. 2014;71(2):180–7.PubMedPubMedCentralCrossRef
49.
Henjum K, Almdahl IS, Arskog V, Minthon L, Hansson O, Fladby T, et al. Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease. Alzheimers Res Ther. 2016;8(1):17.PubMedPubMedCentralCrossRef
50.
Liu D, Cao B, Zhao Y, Huang H, McIntyre RS, Rosenblat JD, et al. Soluble TREM2 changes during the clinical course of Alzheimer's disease: a meta-analysis. Neurosci Lett. 2018;686:10–6.PubMedCrossRef
51.
Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Mansson JE, et al. Cerebrospinal fluid microglial markers in Alzheimer's disease: elevated chitotriosidase activity but lack of diagnostic utility. NeuroMolecular Med. 2011;13(2):151–9.PubMedCrossRef
52.
Westin K, Buchhave P, Nielsen H, Minthon L, Janciauskiene S, Hansson O. CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. PLoS One. 2012;7(1):e30525.PubMedPubMedCentralCrossRef
53.
Brosseron F, Traschutz A, Widmann CN, Kummer MP, Tacik P, Santarelli F, et al. Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer's disease. Alzheimers Res Ther. 2018;10(1):25.PubMedPubMedCentralCrossRef
54.
Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Bouwman F, Venturelli E, et al. Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol. 2006;63(4):538–43.PubMedCrossRef
55.
Blasko I, Lederer W, Oberbauer H, Walch T, Kemmler G, Hinterhuber H, et al. Measurement of thirteen biological markers in CSF of patients with Alzheimer's disease and other dementias. Dement Geriatr Cogn Disord. 2006;21(1):9–15.PubMedCrossRef
56.
Lidstrom AM, Hesse C, Rosengren L, Fredman P, Davidsson P, Blennow K. Normal levels of clusterin in cerebrospinal fluid in Alzheimer's disease, and no change after acute ischemic stroke. J Alzheimers Dis. 2001;3(5):435–42.PubMedCrossRef
57.
Prikrylova Vranova H, Henykova E, Mares J, Kaiserova M, Mensikova K, Vastik M, et al. Clusterin CSF levels in differential diagnosis of neurodegenerative disorders. J Neurol Sci. 2016;361:117–21.PubMedCrossRef
58.
Richens JL, Vere KA, Light RA, Soria D, Garibaldi J, Smith AD, et al. Practical detection of a definitive biomarker panel for Alzheimer's disease; comparisons between matched plasma and cerebrospinal fluid. Int J Mol Epidemiol Genet. 2014;5(2):53–70.PubMedPubMedCentral
59.
Yang C, Wang H, Li C, Niu H, Luo S, Guo X. Association between clusterin concentration and dementia: a systematic review and meta-analysis. Metab Brain Dis. 2018.
60.
Kleinberger G, Yamanishi Y, Suarez-Calvet M, Czirr E, Lohmann E, Cuyvers E, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 2014, 6, 243:243ra86.
61.
Puchades M, Hansson SF, Nilsson CL, Andreasen N, Blennow K, Davidsson P. Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. Brain Res Mol Brain Res. 2003;118(1–2):140–6.PubMedCrossRef
62.
Heslegrave A, Heywood W, Paterson R, Magdalinou N, Svensson J, Johansson P, et al. Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease. Mol Neurodegener. 2016;11:3.PubMedPubMedCentralCrossRef
63.
Piccio L, Deming Y, Del-Aguila JL, Ghezzi L, Holtzman DM, Fagan AM, et al. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol. 2016;131(6):925–33.PubMedPubMedCentralCrossRef
64.
Deming Y, Black K, Carrell D, Cai Y, Del-Aguila JL, Fernandez MV, et al. Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40. BMC Neurol. 2016;16(1):217.PubMedPubMedCentralCrossRef
65.
Nilselid AM, Davidsson P, Nagga K, Andreasen N, Fredman P, Blennow K. Clusterin in cerebrospinal fluid: analysis of carbohydrates and quantification of native and glycosylated forms. Neurochem Int. 2006;48(8):718–28.PubMedCrossRef
66.
Selnes P, Fjell AM, Gjerstad L, Bjornerud A, Wallin A, Due-Tonnessen P, et al. White matter imaging changes in subjective and mild cognitive impairment. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2012;8(5 Suppl):S112–21.CrossRef
67.
Kalheim LF, Fladby T, Coello C, Bjornerud A, Selnes P. [18F]-Flutemetamol uptake in cortex and white matter: comparison with cerebrospinal fluid biomarkers and [18F]-Fludeoxyglucose. J Alzheimers Dis. 2018;62(4):1595–607.PubMedPubMedCentralCrossRef
68.
Sjogren M, Vanderstichele H, Agren H, Zachrisson O, Edsbagge M, Wikkelso C, et al. Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values. Clin Chem. 2001;47(10):1776–81.PubMed
69.
Warrington EK, James M. The visual object and space perception battery. Thames Valley Test Company: Bury St Edmunds, England; 1991.
70.
Heaton RK. Revised COmprehensive norms for an expanded Halstead-Reitan battery: demographically adjusted neuropsychological norms for African American and Caucasian adults: professional manual: psychological assessment resources; 2004.
71.
Sotaniemi M, Pulliainen V, Hokkanen L, Pirttila T, Hallikainen I, Soininen H, et al. CERAD-neuropsychological battery in screening mild Alzheimer's disease. Acta Neurol Scand. 2012;125(1):16–23.PubMedCrossRef
72.
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–72.PubMedCrossRef
73.
Reisberg B, Ferris SH, de Leon MJ, Crook T. Global Deterioration Scale (GDS). Psychopharmacol Bull. 1988;24(4):661–3.PubMed
74.
75.
Hoeijmakers L, Heinen Y, van Dam AM, Lucassen PJ, Korosi A. Microglial priming and Alzheimer's disease: a possible role for (early) immune challenges and epigenetics? Front Hum Neurosci. 2016;10:398.PubMedPubMedCentralCrossRef
76.
Morgan D. The role of microglia in antibody-mediated clearance of amyloid-beta from the brain. CNS Neurol Disord Drug Targets. 2009;8(1):7–15.PubMedCrossRef
77.
Jansen WJ, Ossenkoppele R, Tijms BM, Fagan AM, Hansson O, Klunk WE, et al. Association of Cerebral Amyloid-beta Aggregation with Cognitive Functioning in persons without dementia. JAMA psychiatry. 2018;75(1):84–95.PubMedCrossRef
78.
Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TL, et al. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med. 2014;6(226):226ra30.
79.
Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, et al. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci U S A. 1998;95(18):10896–901.PubMedPubMedCentralCrossRef
80.
Hulshof S, van Haastert ES, Kuipers HF, van den Elsen PJ, De Groot CJ, van der Valk P, et al. CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis. J Neuropathol Exp Neurol. 2003;62(9):899–907.PubMedCrossRef
81.
Maciejewski-Lenoir D, Chen S, Feng L, Maki R, Bacon KB. Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. J Immunol. 1999;163(3):1628–35.PubMed
82.
Hughes PM, Botham MS, Frentzel S, Mir A, Perry VH. Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Glia. 2002;37(4):314–27.PubMedCrossRef
83.
Yoshida H, Imaizumi T, Fujimoto K, Matsuo N, Kimura K, Cui X, et al. Synergistic stimulation, by tumor necrosis factor-alpha and interferon-gamma, of fractalkine expression in human astrocytes. Neurosci Lett. 2001;303(2):132–6.PubMedCrossRef
84.
Mills JH, Alabanza LM, Mahamed DA, Bynoe MS. Extracellular adenosine signaling induces CX3CL1 expression in the brain to promote experimental autoimmune encephalomyelitis. J Neuroinflammation. 2012;9:193.PubMedPubMedCentralCrossRef
85.
Kalehua AN, Nagel JE, Whelchel LM, Gides JJ, Pyle RS, Smith RJ, et al. Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration. Exp Cell Res. 2004;297(1):197–211.PubMedCrossRef
86.
Wittendorp MC, Boddeke HW, Biber K. Adenosine A3 receptor-induced CCL2 synthesis in cultured mouse astrocytes. Glia. 2004;46(4):410–8.PubMedCrossRef
87.
Dicou E, Vincent JP, Mazella J. Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line. J Neurosci Res. 2004;78(1):92–9.PubMedCrossRef
88.
Banisadr G, Gosselin RD, Mechighel P, Kitabgi P, Rostene W, Parsadaniantz SM. Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: evidence for its colocalization with neurotransmitters and neuropeptides. J Comp Neurol. 2005;489(3):275–92.PubMedCrossRef
89.
Bonneh-Barkay D, Bissel SJ, Kofler J, Starkey A, Wang G, Wiley CA. Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathol. 2012;22(4):530–46.PubMedCrossRef
90.
de Silva HV, Harmony JA, Stuart WD, Gil CM, Robbins J. Apolipoprotein J: structure and tissue distribution. Biochemistry. 1990;29(22):5380–9.PubMedCrossRef
91.
Liu L, Persson JK, Svensson M, Aldskogius H. Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection. Glia. 1998;23(3):221–38.PubMedCrossRef
92.
Kullberg S, Aldskogius H, Ulfhake B. Microglial activation, emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS, with special reference to the spinal cord. Brain Res. 2001;899(1–2):169–86.PubMedCrossRef
93.
Charnay Y, Imhof A, Vallet PG, Hakkoum D, Lathuiliere A, Poku N, et al. Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience. 2008;155(3):714–24.PubMedCrossRef
94.
Danik M, Chabot JG, Hassan-Gonzalez D, Suh M, Quirion R. Localization of sulfated glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization. J Comp Neurol. 1993;334(2):209–27.PubMedCrossRef
95.
O'Bryan MK, Cheema SS, Bartlett PF, Murphy BF, Pearse MJ. Clusterin levels increase during neuronal development. J Neurobiol. 1993;24(4):421–32.PubMedCrossRef
96.
Frank S, Burbach GJ, Bonin M, Walter M, Streit W, Bechmann I, et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia. 2008;56(13):1438–47.PubMedCrossRef
97.
Takahashi K, Rochford CD, Neumann H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005;201(4):647–57.PubMedPubMedCentralCrossRef
98.
Jiang T, Tan L, Zhu XC, Zhang QQ, Cao L, Tan MS, et al. Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer's disease. Neuropsychopharmacology. 2014;39(13):2949–62.PubMedPubMedCentralCrossRef
99.
Jiang T, Yu JT, Zhu XC, Tan MS, Gu LZ, Zhang YD, et al. Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice. Neurobiol Aging. 2014;35(6):1243–51.PubMedCrossRef
100.
Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000;164(10):4991–5.PubMedCrossRef
Metadata
Title
Glial activation and inflammation along the Alzheimer’s disease continuum
Authors
Kaja Nordengen
Bjørn-Eivind Kirsebom
Kristi Henjum
Per Selnes
Berglind Gísladóttir
Marianne Wettergreen
Silje Bøen Torsetnes
Gøril Rolfseng Grøntvedt
Knut K. Waterloo
Dag Aarsland
Lars N. G. Nilsson
Tormod Fladby
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1399-2

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