title: Topographical APOE ɛ4 Genotype Influence on Cerebral Metabolism in the Continuum of Alzheimer's Disease: Amyloid Burden Adjusted Analysis.
abstract: APOE ɛ4 contributes to Alzheimer's disease (AD) pathogenesis by amyloid-beta (Aβ)-dependent and Aβ-independent processes.
  
  
  
  We investigated the APOE ɛ4 influence on regional cerebral glucose metabolism (rCMglc) in the continuum of AD after Aβ adjustment.
  
  
  
  We included 318 cognitively normal (CN) elderly, 498 mild cognitive impairment (MCI), and 178 AD from the Alzheimer's Disease Neuroimaging Initiative database. They had [18F] florbetapir positron emission tomography (PET) and [18F] fluorodeoxyglucose (FDG)-PET conducted within 3 months of a clinical and cognitive assessment visit and APOE genotype. At first, the rCMglc differences between APOE ɛ4 carriers (ɛ4+) and non-carriers (ɛ4-) were estimated on a voxel-based analysis using a 'two-sample t-test' design. In the second analysis, Aβ was added as covariate.
  
  
  
  In CN, ɛ4+ showed reduced rCMglc compared to ɛ4-in the bilateral frontal, temporal, and the left parietal regions. In MCI, ɛ4+ showed reduced rCMglc compared to ɛ4- in the bilateral posterior parietal, temporal, and left frontal regions. In AD, ɛ4+ showed reduced rCMglc in the left hippocampus, right insular, and right temporal gyrus. However, after Aβ adjustment, the significant differences in the temporal regions were absent in CN and MCI, and none of the areas detected as significant in the first analysis were statistically significant in AD.
  
  
  
  Our study demonstrated that Aβ-independent APOE ɛ4 influence on rCMglc is limited to the parietal and frontal, but not temporal lobes. These results suggest that APOE ɛ4 may predispose for regional vulnerability according to Aβ-independent and Aβ-dependent processes.
authors: Premedical Science, College of Medicine, Chosun University, Gwangju, Korea.
authors: Eun Hyun
authors: EH
authors: Seo
authors: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors: Sang Hoon
authors: SH
authors: Kim
authors: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors: Sang Hag
authors: SH
authors: Park
authors: Department of Laboratory Medicine, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors: Seong-Ho
authors: SH
authors: Kang
authors: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors: Il Han
authors: IH
authors: Choo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4
keywords: APOE; Aβ burden; cerebral glucose metabolism; mild cognitive impairment