Peng Jinzhong, Tang Qin, Li Yilu, Liu Lin, Biswal Bharat Bhusan, Wang Pan
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of China, 2006 Xiyuan Avenue, Chengdu, 611731, China.
Department of Biomedical Engineering, New Jersey Institute of Technology, 607 Fenster Hall, University Height, Newark, NJ, 07102, USA.
Sci Rep. 2025 Mar 3;15(1):7460. doi: 10.1038/s41598-025-90872-w.
Alzheimer's disease (AD) is known to be associated with cortical anatomical atrophy and neurodegeneration across various brain regions. However, the relationships between brain structural changes in AD and gene expression remain unclear. We perform the morphometric similarity network (MSN) analysis to reveal the consistent cortical structural differences in individuals with AD compared to controls, and investigate the associations between brain-wide gene expression and morphometric changes. Furthermore, we identify abnormally MSN-related genes linked to specific cell types as the major contributors to transcriptomic relationships. MSN-related structural changes are located in the lateral ventral prefrontal cortex, temporal pole and medial prefrontal lobe, which are highly associated with the AD's cognitive decline. Analysis of gene expression shows the spatial correlations between AD-related genes and MSN differences. Examination of cell type-specific signature genes indicates that changes in microglia and neuronal transcriptional profiles largely contribute to AD-specific MSN differences. The study map the disease-specific structural alterations in AD down to the cellular level, offering a novel perspective on the linking surface-level changes to molecular mechanisms.
已知阿尔茨海默病（AD）与多个脑区的皮质解剖萎缩和神经退行性变有关。然而，AD脑结构变化与基因表达之间的关系仍不清楚。我们进行形态计量相似性网络（MSN）分析，以揭示AD患者与对照相比一致的皮质结构差异，并研究全脑基因表达与形态计量变化之间的关联。此外，我们将与特定细胞类型相关的异常MSN相关基因确定为转录组关系的主要贡献者。MSN相关的结构变化位于外侧腹侧前额叶皮质、颞极和内侧前额叶叶，这些区域与AD的认知衰退高度相关。基因表达分析显示了AD相关基因与MSN差异之间的空间相关性。对细胞类型特异性特征基因的检查表明，小胶质细胞和神经元转录谱的变化在很大程度上导致了AD特异性MSN差异。该研究将AD中疾病特异性的结构改变映射到细胞水平，为将表面水平的变化与分子机制联系起来提供了新的视角。
