Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
Alzheimers Dement. 2024 May;20(5):3193-3202. doi: 10.1002/alz.13780. Epub 2024 Mar 17.
This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline.
Participants 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.
Hippocampal 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.
Microglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE-NC partially mediate this association.
本研究调查了海马体中小胶质细胞炎症与脑病理学和认知能力下降之间的关系。
参与者接受了年度临床评估并同意捐献大脑。神经病理学评估量化了海马体中的小胶质细胞负担、淀粉样蛋白 β (Aβ)、tau 缠结、边缘性年龄相关性反应 DNA 结合蛋白 43（TDP-43）脑病神经病理变化（LATE-NC）以及其他常见的脑病理学变化。混合效应和线性回归模型检查了小胶质细胞与全球和特定领域认知测量下降之间的关联，以及与脑病理学的单独关联。路径分析估计了小胶质细胞对全球认知的直接和间接影响。
海马体中的小胶质细胞与全球认知，特别是情景记忆、语义记忆和知觉速度的更快下降有关。tau 缠结和 LATE-NC 与小胶质细胞独立相关。其他病理学，包括 Aβ，没有相关性。tau 缠结和 TDP-43 的区域性海马体负担占小胶质细胞与认知下降关联的一半。
海马体中的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。
