T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

Nat Neurosci. 2024 Aug;27(8):1468-1474. doi: 10.1038/s41593-024-01682-8. Epub 2024 Jun 27.

Abstract

Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer's disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer's disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.

MeSH terms

  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloidosis* / pathology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia* / immunology
  • Microglia* / metabolism
  • Microglia* / pathology
  • Myelin Sheath* / metabolism
  • Myelin Sheath* / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology