The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques

Carlo Sala Frigerio(UK Dementia Research Institute), Leen Wolfs(VIB-KU Leuven Center for Brain & Disease Research), Nicola Fattorelli(VIB-KU Leuven Center for Brain & Disease Research), Nicola Thrupp(VIB-KU Leuven Center for Brain & Disease Research), Iryna Voytyuk(VIB-KU Leuven Center for Brain & Disease Research), Inga Schmidt(VIB-KU Leuven Center for Brain & Disease Research), Renzo Mancuso(VIB-KU Leuven Center for Brain & Disease Research), Wei-Ting Chen(VIB-KU Leuven Center for Brain & Disease Research), Maya E. Woodbury(AbbVie (United States)), Gyan Srivastava(AbbVie (United States)), Thomas Möller(AbbVie (United States)), Eloïse Hudry(Harvard University), Sudeshna Das(Harvard University), Takaomi C. Saido(RIKEN Center for Brain Science), Eric Karran(AbbVie (United States)), Bradley T. Hyman(Harvard University), V. Hugh Perry(UK Dementia Research Institute), Mark Fiers(VIB-KU Leuven Center for Brain & Disease Research), Bart De Strooper(UK Dementia Research Institute)
Cell Reports
April 1, 2019
10.1016/j.celrep.2019.03.099
Cited by 969Open Access
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Abstract

mice over time demonstrate that progressive amyloid-β accumulation accelerates two main activated microglia states that are also present during normal aging. Activated response microglia (ARMs) are composed of specialized subgroups overexpressing MHC type II and putative tissue repair genes (Dkk2, Gpnmb, and Spp1) and are strongly enriched with Alzheimer's disease (AD) risk genes. Microglia from female mice progress faster in this activation trajectory. Similar activated states are also found in a second AD model and in human brain. Apoe, the major genetic risk factor for AD, regulates the ARMs but not the interferon response microglia (IRMs). Thus, the ARMs response is the converging point for aging, sex, and genetic AD risk factors.

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