Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
Department of Nuclear Medicine, Sygehus Lillebaelt, Vejle, Denmark.
Alzheimers Dement. 2024 Nov;20(11):8028-8037. doi: 10.1002/alz.14298. Epub 2024 Oct 11.
Microglial 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.
In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent C-PK11195 and C-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.
Aβ 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.
As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition.
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.
小胶质细胞反应是阿尔茨海默病（AD）病理学的一个组成部分，与淀粉样蛋白β（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。
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 C-PK11195 和 C-Pittsburgh 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分。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。
Aβ负荷和小胶质细胞反应在基线时均独立地对整体认知表现产生不利影响；然而，在 2 年随访时，Aβ负荷与整体认知评分之间的关联部分被小胶质细胞反应所介导。
随着 AD 的进展，相关的小胶质细胞反应部分介导了聚集的 Aβ对认知的有害影响。
这是一项关于淀粉样蛋白β（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影响早期阿尔茨海默病的认知。小胶质细胞反应部分介导了 Aβ对认知的影响在后期阶段。
