title: Effects of APOE promoter polymorphism on the topological organization of brain structural connectome in nondemented elderly.
abstract: The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with noncarriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD.
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Ni
authors: N
authors: Shu
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Xin
authors: X
authors: Li
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Chao
authors: C
authors: Ma
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Junying
authors: J
authors: Zhang
authors: BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.|Banner Alzheimer's Institute, Phoenix, Arizona.
authors: Kewei
authors: K
authors: Chen
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Ying
authors: Y
authors: Liang
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Yaojing
authors: Y
authors: Chen
authors: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People's Republic of China.|BABRI Centre, Beijing Normal University, Beijing, People's Republic of China.
authors: Zhanjun
authors: Z
authors: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E
keywords: APOE promoter; brain connectome; cognition; diffusion MRI; graph theory