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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

Cell Reports · 2019 · ▲ 981 citations

Genomic instability Human Mouse

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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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Provenance

Source: OpenAlex
DOI: 10.1016/j.celrep.2019.03.099
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Fetched: 2026-07-25 MST

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APA

Frigerio, C.S., Wolfs, L., Fattorelli, N., Thrupp, N., Voytyuk, I., Schmidt, I., Mancuso, R., Chen, W., Woodbury, M.E., Srivastava, G., Möller, T., Hudry, E., Das, S., Saido, T.C., Karran, E., Hyman, B.T., Perry, V.H., Fiers, M., & Strooper, B.D. (2019). The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques. <em>Cell Reports</em>. https://doi.org/10.1016/j.celrep.2019.03.099

Vancouver

Frigerio CS, Wolfs L, Fattorelli N, Thrupp N, Voytyuk I, Schmidt I, et al. The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques. Cell Reports. 2019. doi:10.1016/j.celrep.2019.03.099.

BibTeX

@article{carlo2019TheMaj, title = {The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques}, author = {Carlo Sala Frigerio and Leen Wolfs and Nicola Fattorelli and Nicola Thrupp and Iryna Voytyuk and Inga Schmidt and Renzo Mancuso and Wei-Ting Chen and Maya E. Woodbury and Gyan Srivastava and Thomas Möller and Eloïse Hudry and Sudeshna Das and Takaomi C. Saido and Eric Karran and Bradley T. Hyman and V. Hugh Perry and Mark Fiers and Bart De Strooper}, journal = {Cell Reports}, year = {2019}, doi = {10.1016/j.celrep.2019.03.099}, }