Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Nat Neurosci. 2024 Aug;27(8):1468-1474. doi: 10.1038/s41593-024-01682-8. Epub 2024 Jun 27.
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.
年龄相关性髓鞘损伤会引发炎症反应,但尽管年龄是阿尔茨海默病的一个主要风险因素,其在阿尔茨海默病中的作用仍不确定。我们使用阿尔茨海默病的小鼠模型发现,淀粉样蛋白本身会引发与年龄相关的少突胶质细胞和髓鞘损伤。从机制上讲,CD8 T 细胞促进异常干扰素激活的小胶质细胞的进行性积累,这些小胶质细胞具有髓鞘损伤活性。因此,我们的数据表明,针对形成髓鞘的少突胶质细胞的免疫反应可能导致伴有淀粉样蛋白的神经退行性疾病。