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

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, MA] : Cell Press, c 2012-
    • Subject Terms:
      Disease Models, Animal*; Aging/*pathology ; Alzheimer Disease/*pathology ; Biomarkers/*metabolism ; Brain/*pathology ; Microglia/*pathology ; Plaque, Amyloid/*pathology; Aging/genetics ; Aging/metabolism ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/physiology ; Animals ; Biomarkers/analysis ; Brain/metabolism ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Mice, Transgenic ; Microglia/metabolism ; Plaque, Amyloid/genetics ; Plaque, Amyloid/metabolism ; Presenilins/physiology ; Sex Characteristics
    • Abstract:
      Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus of male and female App NL-G-F 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.
      (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Comments:
      Comment in: Nat Rev Neurol. 2019 Jul;15(7):369. (PMID: 31086265)
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    • Grant Information:
      P30 AG062421 United States AG NIA NIH HHS; RF1 AG058674 United States AG NIA NIH HHS; P50 AG005134 United States AG NIA NIH HHS; United Kingdom WT_ Wellcome Trust; R01 AG034504 United States AG NIA NIH HHS; R01 AG041232 United States AG NIA NIH HHS
    • Contributed Indexing:
      Keywords: ARM; Alzheimer; IRM; apoe; app knock in; in situ RNA hybridization; microglia; single cell RNA-seq; single cell sequencing
    • Accession Number:
      0 (Amyloid beta-Peptides)
      0 (Amyloid beta-Protein Precursor)
      0 (Biomarkers)
      0 (Presenilins)
    • Publication Date:
      Date Created: 20190425 Date Completed: 20200617 Latest Revision: 20240211
    • Publication Date:
      20240211
    • Accession Number:
      PMC7340153
    • Accession Number:
      10.1016/j.celrep.2019.03.099
    • Accession Number:
      31018141