Yin Wenwen, Li Zhiwei, Zheng Wenhui, Zhou Xia, Wan Ke, Tang Yating, Cao Jing, Zhao Han, Zhu Xiaoqun, Sun Zhongwu
Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
Eur Arch Psychiatry Clin Neurosci. 2024 Dec 28. doi: 10.1007/s00406-024-01953-2.
The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) gene polymorphism (rs638405) has been widely reported to be associated with Alzheimer's disease (AD) risk. However, studies on the relationship between BACE1 gene polymorphism (rs638405), brain volume, and cognition in AD patients remain scarce. To investigate the effect of genetic polymorphism in BACE1 on gray matter volume (GMV) and cognition in AD, this study recruited 111 cognitively unimpaired (CU) controls and 144 AD patients. The effect of BACE1 rs638405 polymorphism on cognition was explored in CU and AD groups. Then the interaction effect of the diagnosis and BACE1 rs638405 polymorphism on GMV was performed, following the post-hoc analysis of regions of interest (ROIs) in interaction analysis. Mediation analysis was used to elucidate the relationship among genotypes, ROIs and cognition. BACE1 rs638405 G carriers (BACE1 G+) showed significantly lower scores in global cognition and memory function than noncarriers (BACE1 G-) in AD group. Genotypes (G+/G-) and diagnosis (CU/AD) have interaction on GMV of medial temporal lobe (MTL) including the left parahippocampus and right hippocampus. Post-hoc analysis revealed that BACE1 G+ exhibited significantly lower GMV in ROIs compared to BACE1 G- in AD. Finally, mediation analysis further demonstrated that the GMV of ROIs mediated the effect of BACE1 rs638405 polymorphism on cognition in AD. Our results emphasize the BACE1 rs638405 gene polymorphisms may affect the GMV of MTL and cognition in AD, deepening the understanding of AD pathogenesis.
β位点淀粉样前体蛋白裂解酶1（BACE1）基因多态性（rs638405）与阿尔茨海默病（AD）风险的关联已被广泛报道。然而，关于BACE1基因多态性（rs638405）与AD患者脑容量及认知之间关系的研究仍然稀少。为了探究BACE1基因多态性对AD患者灰质体积（GMV）及认知的影响，本研究招募了111名认知未受损（CU）对照者和144名AD患者。在CU组和AD组中探究了BACE1 rs638405多态性对认知的影响。然后，在交互分析中对感兴趣区域（ROI）进行事后分析后，进行了诊断与BACE1 rs638405多态性对GMV的交互作用分析。采用中介分析来阐明基因型、ROI与认知之间的关系。在AD组中，BACE1 rs638405 G携带者（BACE1 G+）在整体认知和记忆功能方面的得分显著低于非携带者（BACE1 G-）。基因型（G+/G-）和诊断（CU/AD）对包括左侧海马旁回和右侧海马在内的内侧颞叶（MTL）的GMV有交互作用。事后分析显示，与AD组中的BACE1 G-相比，BACE1 G+在ROI中的GMV显著更低。最后，中介分析进一步表明，ROI的GMV介导了BACE1 rs638405多态性对AD患者认知的影响。我们的结果强调，BACE1 rs638405基因多态性可能影响AD患者MTL的GMV及认知，加深了对AD发病机制的理解。
