Association of a GSK-3β polymorphism with brain resting-state function in amnestic-type mild cognitive impairment.
The glycogen synthase kinase-3β (GSK-3β) 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-3β 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-3β 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-3β 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-3βrs334558 locus in ways that are distinguishable from controls.
Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, and The Institute of Neuropsychiatry of Southeast University, Nanjing, China.
Feng
F
Bai
Yongmei
Y
Shi
Yonggui
Y
Yuan
Chunxian
C
Yue
Liying
L
Zhuang
Xiaohui
X
Xu
Xiaoyan
X
Liu
Zhijun
Z
Zhang
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000647:Amnesia / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic
C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3