The association between genetic variations and morphology‐based brain networks changes in Alzheimer's disease

功能磁共振成像 神经影像学 神经科学 脑形态计量学 阿尔茨海默病 疾病 颞叶皮质 阿尔茨海默病神经影像学倡议 基因 遗传关联 生物 影像遗传学 心理学 磁共振成像 遗传学 医学 单核苷酸多态性 病理 基因型 放射科
作者
Weixue Xiong,Jiahui Cai,Bo Sun,Henghui Lin,Chiyu Wei,Chengcheng Huang,Xiaohui Zhu,Haizhu Tan
出处
期刊:Journal of Neurochemistry [Wiley]
卷期号:168 (8): 1490-1502 被引量:1
标识
DOI:10.1111/jnc.15761
摘要

Alzheimer's disease (AD) is a highly heritable disease. The morphological changes of cortical cortex (such as, cortical thickness and surface area) in AD always accompany by the change of the functional connectivity to other brain regions and influence the short- and long-range brain network connections, causing functional deficits of AD. In this study, the first hypothesis is that genetic variations might affect morphology-based brain networks, leading to functional deficits; the second hypothesis is that protein-protein interaction (PPI) between the candidate proteins and known interacting proteins to AD might exist and influence AD. 600 470 variants and structural magnetic resonance imaging scans from 175 AD patients and 214 healthy controls were obtained from the Alzheimer's Disease Neuroimaging Initiative-1 database. A co-sparse reduced-rank regression model was fit to study the relationship between non-synonymous mutations and morphology-based brain networks. After that, PPIs between selected genes and BACE1, an enzyme that was known to be related to AD, are explored by using molecular dynamics (MD) simulation and co-immunoprecipitation (Co-IP) experiments. Eight genes affecting morphology-based brain networks were identified. The results of MD simulation showed that the PPI between TGM4 and BACE1 was the strongest among them and its interaction was verified by Co-IP. Hence, gene variations influence morphology-based brain networks in AD, leading to functional deficits. This finding, validated by MD simulation and Co-IP, suggests that the effect is robust.
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