Abstract:
The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer\'s disease (AD). We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns. Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD. Our results showed that the hippocampus and amygdala exhibit the most severe atrophy, followed by the temporal, frontal, and occipital lobes in mild cognitive impairment (MCI) and AD. The extent of atrophy in MCI was less severe than that in AD. A series of biological processes related to the glutamate signaling pathway, cellular stress response, and synapse structure and function were investigated through gene set enrichment analysis. Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy, providing new insight for further clinical research on AD.
摘要:
本研究旨在评估阿尔茨海默病(AD)对区域性脑萎缩的易感性及其生物学机制。我们进行了数据驱动的荟萃分析,将来自三个数据集的3,118张结构磁共振图像进行组合,以获得稳健的萎缩模式。然后,我们引入了一组放射基因组分析,以研究AD萎缩模式的生物学基础。我们的结果表明海马体和杏仁核表现出最严重的萎缩,其次是时间,额叶,轻度认知障碍(MCI)和AD的枕叶。MCI的萎缩程度不如AD严重。与谷氨酸信号通路相关的一系列生物学过程,细胞应激反应,并通过基因集富集分析研究了突触的结构和功能。我们的研究有助于了解萎缩的表现,并更深入地了解导致萎缩的病理生理过程,为AD的进一步临床研究提供新的见解。