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The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk
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Abstract
Common variants in the microglia-specific MS4A gene cluster modify risk for late-onset Alzheimer’s disease and modulate extracellular soluble TREM2.
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“TREM2 function is regulated via interactions and crosstalk with other receptors, including the AD risk hits CD33, and the Ms4A gene-cluster products [23, 59].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [59]
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In the citing paper
“As Ms4a genes can regulate the level of soluble TREM2 and modify AD risk39, we used immunoblot analysis to rule out the possibility that myelin dysfunction affects TREM2 protein levels or cleavage through increased Ms4a expression (Extended Data Fig. 9a).”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [39]
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“Targeting CSF proteins has proven successful at elucidating causal genes at some disease GWAS loci, including an association for the TREM2 protein at the MS4A locus potentially an Alzheimer’s Disease (AD) risk locus7,20 and an association for GRN protein levels near LRRK2 potentially relevant for Parkinson’s Disease (PD)21.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [7]
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“supporting a strong immunological role in AD93–95 including TREM27,96, CD33, and IL34.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [7]
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“MS4A6A, a gene related to AD risk22,68,69, was one of the genes that showed a region-specific effect of age68,70.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [69]
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“Common variants in the MS4A gene cluster were shown to significantly regulate sTREM2 levels in CSF [134], demonstrating regulation of this endophenotype is orchestrated by genetic variants that also modify risk for disease.”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [134]
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“The introduction of the human TREM2 transgene reduced pathology and rescued cognitive function in amyloidbearing mice (14).”
Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.
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Self-citationSoluble TREM2 induces inflammatory responses and enhances microglial survival
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Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status
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Self-citationExpression of Novel Alzheimer’s Disease Risk Genes in Control and Alzheimer’s Disease Brains
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Self-citationElucidating the Role of TREM2 in Alzheimer’s Disease
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Coding variants in TREM2 increase risk for Alzheimer's disease
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“In addition to the full-length TREM2, which makes up part of a transmembrane receptor, a soluble form of TREM2 (sTREM2) is produced by alternative splicing or proteolytic cleavage of the full-length TREM2 protein (6, 13, 20).”
Self-citationWang, M., Roussos, P., McKenzie, A., Zhou, X., Kajiwara, Y., Brennand, K. J., De Luca, G. C., Crary, J. F., Casaccia, P., Buxbaum, J. D., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0355-3 · Cited by 314 · cited 2×
“The RNA extraction and sequencing methods for the Mayo Clinic cohort and the AMP-AD cohort were as described previously (62, 63).”
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“Given that stimulation of macro phages with interleukin-4 (IL-4) results in up-regulation of TREM2 and MS4A4A (42, 43), we measured sTREM2 in the presence or absence of IL-4 as previously described (27).”
Self-citationIncreased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease
Heslegrave, A., Heywood, W., Paterson, R., Magdalinou, N., Svensson, J., Johansson, P., Öhrfelt, A., Blennow, K., Hardy, J., Schott, J., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0071-x · Cited by 303 · cited 3×
“Our group and others have demonstrated that CSF sTREM2 is elevated in AD (23, 24, 26).”
InfluentialSelf-citationAltered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
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Self-citationBemiller, S. M., McCray, T. J., Allan, K., Formica, S. V., Xu, G., Wilson, G., Kokiko-Cochran, O. N., Crish, S. D., Lasagna-Reeves, C. A., Ransohoff, R. M., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0216-6 · Cited by 299 · cited 1×
“In contrast, studies of tau pathology indicate that Trem2 deficiency protects against neurodegeneration, suggesting a detrimental role for TREM2 in the presence of tau pathology (18, 19).”
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H., & Walter, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517540 · Cited by 296 · cited 1×
“In addition to the full-length TREM2, which makes up part of a transmembrane receptor, a soluble form of TREM2 (sTREM2) is produced by alternative splicing or proteolytic cleavage of the full-length TREM2 protein (6, 13, 20).”
TREM2 regulates microglial cell activation in response to demyelination in vivo
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C. M., Galimberti, D., Olivecrona, G., Klein, R. S., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1388-1 · Cited by 296 · cited 1×
“TREM2 is highly and specifically expressed in microglia in the central nervous system (CNS) where it plays a key role in microglial activation, survival, and phagocytosis ( 8 – 11 ).”
TREM2-Ligand Interactions in Health and Disease
Kober, D. L., & Brett, T. J. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.04.004 · Cited by 284 · cited 1×
“Some evidence suggests that sTREM2 binds to and sequesters TREM2 ligands, such as apolipoproteins, thus preventing these ligands from activating the TREM2 receptor (53, 54).”
Self-citationSuárez-Calvet, M., Araque Caballero, M. Á., Kleinberger, G., Bateman, R. J., Fagan, A. M., Morris, J. C., Levin, J., Danek, A., Ewers, M., Haass, C., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag1767 · Cited by 272 · cited 3×
“In this study, we did not analyze the association of sTREM2 with AD clinical status because previous studies (24, 25) have recently demonstrated that sTREM2 is associated with AD risk.”
Self-citationSchlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., & Haass, C. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707672 · Cited by 266 · cited 2×
“Recently, a cleavage site was identified in TREM2, which can be targeted by proteases such as ADAM10, ADAM17, and -secretase to generate sTREM2 (21, 22).”
Self-citationImpaired Differentiation of Osteoclasts in TREM-2–deficient Individuals
Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A., & Colonna, M. (2003) · Journal of Experimental Medicine · doi:10.1084/jem.20022220 · Cited by 256 · cited 2×
“S9, E, F and H), which is consistent with previous reports (41, 42).”
The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Carmona, S., Zahs, K., Wu, E., Dakin, K., Bras, J., & Guerreiro, R. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30232-1 · Cited by 244 · cited 1×
“Our findings and previous studies indicate that increasing TREM2 or activating the TREM2 signaling pathway could offer a new therapeutic approach for treating AD (45).”
(ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetic Consortium (ADGC), Li, Z., Kapoor, M., Harari, O., Del-Aguila, J. L., Black, K., Carrell, D., Cai, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1685-y · Cited by 231
Self-citationTrabzuni, D., Ryten, M., Walker, R., Smith, C., Imran, S., Ramasamy, A., Weale, M. E., & Hardy, J. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07432.x · Cited by 229 · cited 9×
“Similarly, rs1582763 produced a nominal cis-eQTL effect on MS4A6A expression in GTEx (frontal cortex: = 0.183, P = 0.04; cortex: = 0.165, P = 0.05) and Braineac (medulla: = 0.337, P = 4.50 × 10 −4 ) human brain tissue samples.”
InfluentialTREM2 and the neuroimmunology of Alzheimer's disease
Hickman, S. E., & El Khoury, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.021 · Cited by 221
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.016 · Cited by 219
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207
Self-citationThornton, P., Sevalle, J., Deery, M. J., Fraser, G., Zhou, Y., Ståhl, S., Franssen, E. H., Dodd, R. B., Qamar, S., Gomez Perez‐Nievas, B., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707673 · Cited by 200 · cited 2×
“Recently, a cleavage site was identified in TREM2, which can be targeted by proteases such as ADAM10, ADAM17, and -secretase to generate sTREM2 (21, 22).”
TREM2 in CNS homeostasis and neurodegenerative disease
Painter, M. M., Atagi, Y., Liu, C.-C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0040-9 · Cited by 169 · cited 1×
“Some evidence suggests that sTREM2 binds to and sequesters TREM2 ligands, such as apolipoproteins, thus preventing these ligands from activating the TREM2 receptor (53, 54).”
Variants in TF and HFE Explain ∼40% of Genetic Variation in Serum-Transferrin Levels
Benyamin, B., McRae, A. F., Zhu, G., Gordon, S. D., Henders, A. K., Palotie, A. V., Peltonen, L., Martin, N. G., Montgomery, G. W., Whitfield, J. B., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.11.011 · Cited by 167
TREM2 is associated with the risk of Alzheimer's disease in Spanish population
Benitez, B. A., Cooper, B., Pastor, P., Jin, S.-C., Lorenzo, E., Cervantes, S., & Cruchaga, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.018 · Cited by 163
Self-citationGuerreiro, R., Bilgic, B., Guven, G., Brás, J., Rohrer, J., Lohmann, E., Hanagasi, H., Gurvit, H., & Emre, M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.005 · Cited by 158 · cited 1×
“R47H is also associated with clinical, imaging, and neuropathological AD phenotypes, including advanced behavioral symptoms, gray matter atrophy, and Braak staging (3, 4).”
TREM2 is associated with increased risk for Alzheimer’s disease in African Americans
Jin, S. C., Carrasquillo, M. M., Benitez, B. A., Skorupa, T., Carrell, D., Patel, D., Lincoln, S., Krishnan, S., Kachadoorian, M., Reitz, C., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0016-9 · Cited by 153
Self-citationCerebrospinal fluid soluble TREM2 in aging and Alzheimer’s disease
Henjum, K., Almdahl, I. S., Årskog, V., Minthon, L., Hansson, O., Fladby, T., & Nilsson, L. N. G. (2016) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0182-1 · Cited by 145 · cited 1×
“Recently, a cleavage site was identified in TREM2, which can be targeted by proteases such as ADAM10, ADAM17, and -secretase to generate sTREM2 ( 21 , 22 ). sTREM2 is released into the cerebrospinal fluid (CSF) where it can be quantified ( 13 , 23 – 28 ).”
Cruchaga, C., Kauwe, J. S. K., Mayo, K., Spiegel, N., Bertelsen, S., Nowotny, P., Shah, A. R., Abraham, R., Hollingworth, P., Harold, D., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001101 · Cited by 128
Self-citationAlzheimer’s disease risk polymorphisms regulate gene expression in the ZCWPW1 and the CELF1 loci
Karch, C. M., Ezerskiy, L. A., Bertelsen, S., Alzheimer’s Disease Genetics Consortium (ADGC), & Goate, A. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148717 · Cited by 111
Self-citationLautner, R., Palmqvist, S., Mattsson, N., Andréasson, U., Wallin, A., Pålsson, E., Jakobsson, J., Herukka, S., Owenius, R., Olsson, B., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1060 · Cited by 110 · cited 1×
“The influence of APOE genotype on A pathology, including CSF A42 concentration, has been a consistent finding (31, 35).”
Self-citationMS4A4A: a novel cell surface marker for M2 macrophages and plasma cells
Sanyal, R., Polyak, M. J., Zuccolo, J., Puri, M., Deng, L., Roberts, L., Zuba, A., Storek, J., Luider, J. M., Sundberg, E. M., et al. (2017) · Immunology and Cell Biology · doi:10.1038/icb.2017.18 · Cited by 99 · cited 6×
“TREM2 and MS4A4A are both highly and specifically expressed in human microglia ( 38 ).”
InfluentialChang, T., & Chen, J. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0439-9 · Cited by 87
Johansson, P., Mattsson, N., Hansson, O., Wallin, A., Johansson, J.-O., Andréasson, U., Zetterberg, H., Blennow, K., & Svensson, J. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101878 · Cited by 71 · cited 1×
“We also evaluated whether CSF sTREM2 was associated with sex, as previously reported ( 24 – 26 , 32 ).”
Self-citationThe Dominantly Inherited Alzheimer Network (DIAN), Li, Z., Del-Aguila, J. L., Dube, U., Budde, J., Martinez, R., Black, K., Xiao, Q., Cairns, N. J., Dougherty, J. D., et al. (2018) · Genome Medicine · doi:10.1186/s13073-018-0551-4 · Cited by 56
Self-citationDeming, Y. K., Li, Z., Benítez, B. A., & Cruchaga, C. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1486823 · Cited by 50 · cited 1×
“Recent evidence from AD animal models suggests that TREM2 has a complex relationship with the key proteins involved in AD pathogenesis, amyloid- (A ) and tau ( 12 ).”
Self-citationRarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States
Wang, L.-S., Naj, A. C., Graham, R., Crane, P. K., Kunkle, B. W., Cruchaga, C., Murcia, J. D. G., Cannon‐Albright, L., Baldwin, C. T., Zetterberg, H., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.2157 · Cited by 47
Self-citationFrontobasal gray matter loss is associated with the TREM2 p.R47H variant
Luis, E. O., Ortega-Cubero, S., Lamet, I., Razquin, C., Cruchaga, C., Benitez, B. A., Lorenzo, E., Irigoyen, J., Pastor, M. A., & Pastor, P. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.007 · Cited by 47
Self-citationKauwe, J. S. K., Cruchaga, C., Bertelsen, S. E., Mayo, K., Latu, W., Nowotny, P., Hinrichs, A. L., Fagan, A. M., Holtzman, D. M., Initiative, A. D. N., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091711 · Cited by 44
Self-citationCui, L., Gao, Y., Xie, Y., Wang, Y., Cai, Y., Shao, X., Ma, X., Li, Y., Ma, G., Liu, G., et al. (2015) · Critical Care · doi:10.1186/s13054-015-0796-x · Cited by 42 · cited 1×
“However, the risk variants in TYROBP are all rare (59, 60), and although there are variants in ADAM10 known to affect the function or expression of ADAM10, these variants also occur infrequently (61).”
Cruse, G., Beaven, M. A., Music, S. C., Bradding, P. H., Gilfillan, A. M., & Metcalfe, D. D. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-07-1221 · Cited by 41 · cited 2×
“Whereas the function of MS4A4A in the brain is poorly understood, it may be involved in protein trafficking and clathrin-dependent endocytosis (44).”
Garge, N., Pan, H., Rowland, M. D., Cargile, B. J., Zhang, X., Cooley, P. C., Page, G. P., & Bunger, M. K. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900378-mcp200 · Cited by 36
Rodgers, K. M., Deming, Y. K., Bercum, F. M., Chumachenko, S. Y., Wieseler, J. L., Johnson, K. W., Watkins, L. R., & Barth, D. S. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.3090 · Cited by 33
Self-citationGenetic studies of plasma analytes identify novel potential biomarkers for several complex traits
Deming, Y., Xia, J., Cai, Y., Lord, J., Del-Aguila, J. L., Fernandez, M. V., Carrell, D., Black, K., Budde, J., Ma, S., et al. (2016) · Scientific Reports · doi:10.1038/srep18092 · Cited by 28
Self-citationBenítez, B. A., & Sands, M. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-06710-1 · Cited by 23 · cited 2×
“Lentivirus vector preparation and experiments Lentiviral vectors encoding human MS4A4A WT cDNA (NM_148975) Myc-DDK-tagged (RC204646L1), GFP (PS100071), the shRNA for MS4A4A (pGFP-C-shLenti MS4A4A (TL303135B), and the control shRNA pGFP-C-shLenti Scrambled (TR30021) were obtained from OriGene and produced as previously…”
Li, Z., Del‐Aguila, J. L., Dube, U., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/266296 · Cited by 3
Self-citationPanoutsopoulou, K., Thiagarajah, S., Day-Williams, A., Southam, L., Hatzikotoulas, K., Matchan, A., Doherty, M., Wilkinson, J. M., & Zeggini, E. (2014) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2014.02.447 · Cited by 1
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Large-scale integration of the plasma proteome with genetics and disease
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The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway
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Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Depp, C., Sun, T., Sasmita, A. O., Spieth, L., Berghoff, S. A., Nazarenko, T., Overhoff, K., Steixner-Kumar, A. A., Subramanian, S., Arinrad, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06120-6 · Cited by 493
Self-citationMeningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Da Mesquita, S., Papadopoulos, Z., Dykstra, T., Brase, L., Farias, F. G., Wall, M., Jiang, H., Kodira, C. D., de Lima, K. A., Herz, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03489-0 · Cited by 431
Self-citation
Metadata
- Authors
- Deming, Y., Filipello, F., Cignarella, F., Cantoni, C., Hsu, S., Mikesell, R., Li, Z., Del-Aguila, J. L., Dube, U., Farias, F. G., Bradley, J., Budde, J., Ibanez, L., Fernandez, M. V., Blennow, K., Zetterberg, H., Heslegrave, A., Johansson, P. M., Svensson, J., Nellgård, B., Lleo, A., Alcolea, D., Clarimon, J., Rami, L., Molinuevo, J. L., Suárez-Calvet, M., Morenas-Rodríguez, E., Kleinberger, G., Ewers, M., Harari, O., Haass, C., Brett, T. J., Benitez, B. A., Karch, C. M., Piccio, L., & Cruchaga, C.
- Affiliations
- University of Wisconsin–Madison (US)
- Washington University in St. Louis (US)
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
- Lund University (SE)
- Sahlgrenska University Hospital (SE)
- Universitat Autònoma de Barcelona (ES)
- Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Pasqual Maragall Foundation (ES)
- Munich Cluster for Systems Neurology (DE)
- IDIBAPS, Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic, Barcelona, Spain.
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
- Biomedical Center (BMC), Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
- German Center for Neurodegenerative Diseases (DE)
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
- Corresponding author
- Deming, Yuetiva
- Filipello, Fabia
- Cignarella, Francesca
- Harari, Oscar
- Haass, Christian
- Karch, Celeste M.
- ORCID
- Deming, Yuetiva
- Filipello, Fabia
- Cignarella, Francesca
- Cantoni, Claudia
- Hsu, Simon
- Mikesell, Robert
- Li, Zeran
- Del-Aguila, Jorge L
- Dube, Umber
- Farias, Fabiana Geraldo
- Bradley, Joseph
- Budde, John
- Ibanez, Laura
- Fernandez, Maria Victoria
- Blennow, Kaj
- Zetterberg, Henrik
- Heslegrave, Amanda
- Johansson, Per M
- Svensson, Johan
- Nellgård, Bengt
- Alcolea, Daniel
- Clarimon, Jordi
- Rami, Lorena
- Suárez-Calvet, Marc
- Kleinberger, Gernot
- Ewers, Michael
- Harari, Oscar
- Haass, Christian
- Benitez, Bruno A.
- Karch, Celeste M.
- Piccio, Laura
- Cruchaga, Carlos
- Venue
- Science Translational Medicine
- Published
- 2019-08-14
- Volume
- 11
- Issue
- 505
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6697053
- OpenAlex
- W2968181515
- Cited by
- 271
- References
- 90
- Citations by year
- 2026: 21 · 2025: 37 · 2024: 46 · 2023: 43 · 2022: 48 · 2021: 40 · 2020: 21 · 2019: 15
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science Translational Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- National Institutes of Health (R01AG044546, P01AG003991, RF1AG053303, R01AG058501, R01AG035083)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- soluble TREM2, Alzheimer's disease risk, late-onset Alzheimer's disease, microglia, common genetic variants, genetic risk factors
- MeSH terms
- Alzheimer Disease, Female, Multigene Family, Humans, Macrophages, Male, Membrane Glycoproteins, Membrane Proteins, Receptors, Immunologic, Meta-Analysis as Topic, Genome-Wide Association Study
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