Association of a GSK-3 beta Polymorphism with Brain Resting-State Function in Amnestic-Type Mild Cognitive Impairment

作者：Bai Feng; Shi Yongmei; Yuan Yonggui; Yue Chunxian; Zhuang Liying; Xu Xiaohui; Liu Xiaoyan; Zhang Zhijun^*

来源：Journal of Alzheimer's Disease, 2012, 32(2): 387-396.

DOI：10.3233/JAD-2012-120631

• Brain function
• functional magnetic resonance imaging
• genetic imaging
• glycogen synthase kinase
• mild cognitive impairment
• resting state

The glycogen synthase kinase-3 beta (GSK-3 beta) gene has been implicated in Alzheimer';s disease (AD). Polymorphisms in this gene are plausible modulators of brain function. However, little is known about the potential role of the GSK-3 beta rs334558 polymorphism, which has been associated with amnestic mild cognitive impairment (aMCI), which is itself associated with a high risk of AD. In this study, 43 aMCI patients and 30 healthy controls underwent resting-state functional magnetic resonance imaging, and their GSK-3 beta rs334558 genotypes were evaluated to determine the effect of the risk variant on regional brain activity and functional networks in these subjects. Then, gene-brain-behavior relationships were examined. Compared with the controls, aMCI subjects with the higher risk T allele had more deficits in regional activation of the right superior frontal gyrus (rSFG), while a higher functional connectivity of the rSFG was observed in TT/CT carriers. Further correlative analyses revealed that the increase in rSFG connectivity was robustly positively correlated with non-memory performance in aMCI GSK-3 beta rs334558 TT/CT carriers. Our findings are the first to show that a clinically significant proportion of resting-state brain function variation in aMCI patients may be explained by genetic variation at the GSK-3 beta rs334558 locus in ways that are distinguishable from controls.

• 出版日期2012
• 单位东南大学