title: Differential Effects of APOE Genotypes on the Anterior and Posterior Subnetworks of Default Mode Network in Amnestic Mild Cognitive Impairment.
abstract: The apolipoprotein E (APOE) ɛ4 carriers are at increased risk of developing Alzheimer's disease (AD) while the ɛ2 carriers appear to be protected against the disease. The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), consists of functionally differentiable anterior and posterior subnetworks.
  
  
  
  This study was to investigate whether there are differential effects of APOE polymorphisms on DMN subnetworks in amnestic mild cognitive impairment (aMCI).
  
  
  
  Functional connectivity (FC) analyses were performed in DMN subnetworks in 74 aMCI (9 APOE ɛ2ɛ3, 44 ɛ3ɛ3, and 21 ɛ3ɛ4) and 105 healthy controls (HC; 32 APOE ɛ2ɛ3, 39 ɛ3ɛ3, and 34 ɛ3ɛ4). Logistic regression analysis was performed to obtain a model for classifying aMCI and HC.
  
  
  
  Significant interactions of APOE by aMCI on FCs were found in right cerebellum posterior lobe, left lingual gyrus, and right middle cingulate cortex in the vmPFC subnetwork, and bilateral fusiform gyrus, left inferior frontal gyrus, and left precuneus in the PCC subnetwork. The impairment of episodic memory for ɛ4-carriers in aMCI negatively correlated with altered FC between vmPFC and right middle cingulate cortex, while positively correlated with altered FC between PCC and left fusiform gyrus. A model composed of episodic memory and FCs dexterity correctly classified 89.4% of aMCI and HC.
  
  
  
  APOE ɛ4 and ɛ2 alleles differentially mediate anterior and posterior DMN subnetworks. Furthermore, it further suggests that the anterior and posterior DMN subnetworks in aMCI play an opposing role on the impairment of episodic memory.
authors: Baoyu
authors: B
authors: Yuan
authors: Chunming
authors: C
authors: Xie
authors: Hao
authors: H
authors: Shu
authors: Wenxiang
authors: W
authors: Liao
authors: Zan
authors: Z
authors: Wang
authors: Duan
authors: D
authors: Liu
authors: Zhijun
authors: Z
authors: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002531:Cerebellum / Q000000981:diagnostic imaging; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging*
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4
keywords: Amnesic mild cognitive impairment; default mode network; episodic memory; functional MRI; functional connectivity; posterior cingulated cortex; ventromedial prefrontal cortex