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

  • Shreeya Kedia,
  • Hao Ji,
  • Ruoqing Feng,
  • Peter Androvic,
  • Lena Spieth,
  • Lu Liu,
  • Jonas Franz,
  • Hanna Zdiarstek,
  • Katrin Perez Anderson,
  • Cem Kaboglu,
  • Qian Liu,
  • Nicola Mattugini,
  • Fatma Cherif,
  • Danilo Prtvar,
  • Ludovico Cantuti-Castelvetri,
  • Arthur Liesz,
  • Martina Schifferer,
  • Christine Stadelmann,
  • Sabina Tahirovic,
  • Ozgun Gokce,
  • Mikael Simons

摘要

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.