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

Carlo Sala Frigerio; Leen Wolfs; Nicola Fattorelli; Nicola Thrupp; Iryna Voytyuk; Inga Schmidt; Renzo Mancuso; Wei-Ting Chen; Maya E. Woodbury; Gyan Srivastava; Thomas Möller; Eloïse Hudry; Sudeshna Das; Takaomi C. Saido; Eric Karran; Bradley T. Hyman; V. Hugh Perry; Mark Fiers; Bart De Strooper

doi:10.1016/j.celrep.2019.03.099

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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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Frigerio et al. (2019) studied this question.

synapsesocial.com/papers/6a6f8f6175498292b708f11c https://doi.org/10.1016/j.celrep.2019.03.099

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

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

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