INTRODUCTIONThis study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline.METHODSParticipants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age‐related transactive response DNA‐binding protein 43 (TDP‐43) encephalopathy neuropathologic changes (LATE‐NC), and other common brain pathologies. Mixed‐effect and linear regression models examined the association of microglia with a decline in global and domain‐specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition.RESULTHippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE‐NC were independently associated with microglia. Other pathologies, including Aβ, were not related. Regional hippocampal burden of tau tangles and TDP‐43 accounted for half of the association of microglia with cognitive decline.DISCUSSIONMicroglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE‐NC partially mediate this association.

中文翻译：

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海马小胶质细胞、AD 和 LATE-NC 与老年人认知能力下降之间的关联

简介本研究调查了海马小胶质细胞炎症、大脑病理和认知能力下降之间的关系。方法参与者接受了年度临床评估并同意大脑捐赠。神经病理学评估量化了海马中的小胶质细胞负荷、β 淀粉样蛋白 (Aβ)、tau 蛋白缠结和边缘年龄相关的交互反应 DNA 结合蛋白 43 (TDP-43) 脑病神经病理变化 (LATE-NC) 和其他常见的脑部病理。混合效应和线性回归模型检查了小胶质细胞与整体和特定领域认知测量下降的关联，并分别与大脑病理学相关。路径分析估计了小胶质细胞对整体认知的直接和间接影响。结果海马小胶质细胞与整体认知的更快下降有关，特别是在情景记忆、语义记忆和知觉速度方面。 Tau 缠结和 LATE-NC 与小胶质细胞独立相关。其他病理，包括 Aβ，不相关。 tau 蛋白缠结和 TDP-43 的区域海马负担占小胶质细胞与认知能力下降关联的一半。讨论海马小胶质细胞炎症导致认知能力下降。 Tau 缠结和 LATE-NC 部分介导了这种关联。