INTRODUCTIONMicroglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.METHODSIn this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11C‐PK11195 and 11C‐Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2‐year follow‐up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed.RESULTSAβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2‐year follow‐up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response.DISCUSSIONAs AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition.Highlights This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance. Aβ and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aβ on cognition in later stages.

中文翻译：

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小胶质细胞反应部分介导 Aβ 对阿尔茨海默病认知的影响


引言胶质细胞反应是阿尔茨海默病 （AD） 病理学的一个组成部分，与 β 淀粉样蛋白 （Aβ） 沉积有关。本研究旨在探讨 Aβ 和小胶质细胞反应对整体认知障碍的影响。方法在这项纵向研究中，28 名轻度认知障碍患者和 11 名健康对照者在基线和 2 年随访时接受了 11C-PK11195 和 11C-匹兹堡化合物 B 正电子发射断层扫描 （PET）、结构磁共振成像扫描和整体认知评级。评估了 PET 摄取与整体认知之间的相关性。此外，还评估了小胶质细胞反应对 Aβ 负荷与整体认知之间关联的中介作用。结果Aβ 负荷和小胶质细胞反应均独立地损害基线时的整体认知能力;然而，在 2 年随访中，Aβ 负荷与整体认知评级之间的关联部分由小胶质细胞反应介导。讨论 AD 进展，相关的小胶质细胞反应部分介导了聚集的 Aβ 对认知的不利影响。亮点 这是一项对 β 淀粉样蛋白 （Aβ）、小胶质细胞反应和整体认知表现的纵向研究。Aβ 和小胶质细胞反应都会影响早期阿尔茨海默病的认知。小胶质细胞反应部分介导 Aβ 对后期认知的影响。