2. Academic Validation
  3. T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

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

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. mikael.simons@dzne.de.
  • 9 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. mikael.simons@dzne.de.
  • 10 Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany. mikael.simons@dzne.de.
  • 11 Munich Cluster of Systems Neurology (SyNergy), Munich, Germany. mikael.simons@dzne.de.
  • # 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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