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

  • Nat Neurosci. 2024 Jun 27. doi: 10.1038/s41593-024-01682-8.
Shreeya Kedia  #  1  2 ,  Hao Ji  #  3 ,  Ruoqing Feng  1  2 ,  Peter Androvic  3  4 ,  Lena Spieth  1  2 ,  Lu Liu  3 ,  Jonas Franz  5 ,  Hanna Zdiarstek  5 ,  Katrin Perez Anderson  3  4 ,  Cem Kaboglu  1  3 ,  Qian Liu  3  4 ,  Nicola Mattugini  1  2 ,  Fatma Cherif  2 ,  Danilo Prtvar  2 ,  Ludovico Cantuti-Castelvetri  1  2 ,  Arthur Liesz  3  6 ,  Martina Schifferer  2  6 ,  Christine Stadelmann  5 ,  Sabina Tahirovic  2 ,  Ozgun Gokce  3  4  6  7 ,  Mikael Simons  8  9  10  11
Affiliations
  • 1. Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • 2. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • 3. Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany.
  • 4. Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • 5. Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • 6. Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
  • 7. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • 8. Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany. [email protected].
  • 9. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. [email protected].
  • 10. Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany. [email protected].
  • 11. Munich Cluster of Systems Neurology (SyNergy), Munich, Germany. [email protected].
  • # Contributed equally.
PMID: 38937583 DOI: 10.1038/s41593-024-01682-8
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.

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