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

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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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Kedia, S., Ji, H., Feng, R., Androvic, P., Spieth, L., Liu, L., … Simons, M. (2024). T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis. Nature Neuroscience, 27(8), 1468–1474. https://doi.org/10.1038/s41593-024-01682-8

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