title: The TT allele of rs405509 synergizes with APOE ε4 in the impairment of cognition and its underlying default mode network in non-demented elderly.
abstract: BACKGROUND
  Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 as the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease (AD). However, it is unclear the APOE-rs405509 interaction effect on brain spontaneous activity.
  
  
  METHODS
  We analyzed the interaction of the rs405509 TT allele and the APOE ε4 allele on cognitive performances measured using neuropsychological tests and brain default mode network (DMN) defined by independent component analysis using based on resting-state functional magnetic resonance imaging data among the non-demented elderly people.
  
  
  RESULTS
  Significant interaction was found between rs405509 and APOE on general mental status, memory and attention (p<0.05). Functional network analysis showed a significantly APOE-rs405509 interaction on anterior cingulate gyrus, medial frontal region and precuneus at anterior and posterior DMN (False Discovery Rate p<0.05). Additionally, significant correlations were found between cognitive performance and DMN connectivity (p<0.05).
  
  
  CONCLUSIONS
  The data indicates that the APOE-rs405509 interaction impairs elderly's cognitive performance through brain functional network.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yaojing
authors.initials: Y
authors.lastname: Chen
authors.forename: Junying
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning& IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China. zhang_rzs@bnu.edu.cn.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012146:Rest
chemical_list: D053327:Apolipoprotein E4