APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge

The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response: two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses in mice expressing human APOE to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNA sequencing (RNA-seq) highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia…

• AC
  American Cancer Society

  Award: 16-182-28
• AA
  Alzheimer's Association
• SB
  St. Baldrick's Foundation
• CA
  Cure Alzheimer's Fund
• NI
  National Institute on Aging

  Awards: T32AG057461, T32GM118292, R01AG080589, R01AG062550-03S1, R01AG066653, R01AG060056, R01AG070830, F31AG076282, RF1NS118558
• NC
  National Cancer Institute

  Award: P30 CA177558