T cell mediated microglia activation triggers myelin pathology in a model of amyloidosis [MERFISH]

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. Brain sections were collected from mouse model of amyloidosis and analyzed by MERFISH

年龄相关性髓鞘损伤可诱发炎症反应，尽管衰老是阿尔茨海默病（Alzheimer's disease）的主要风险因素，但其在该病中的具体作用仍不明确。本研究利用阿尔茨海默病小鼠模型，发现淀粉样蛋白病变（amyloidosis）本身即可触发年龄相关性少突胶质细胞（oligodendrocyte）与髓鞘损伤。从机制层面来看，CD8+ T细胞可促进异常干扰素激活的、具有髓鞘损伤活性的小胶质细胞（microglia）进行性蓄积。综上，本研究数据表明，针对具备髓鞘形成功能的少突胶质细胞的免疫应答，可能参与伴淀粉样蛋白病变的神经退行性疾病的发生发展。研究人员从淀粉样蛋白病变小鼠模型中采集脑组织切片，并通过多重错误稳健荧光原位杂交（MERFISH）技术对其进行分析。