title: The effect of β-amyloid positivity on cerebral metabolism in cognitively normal seniors.
abstract: We evaluated the effect of cerebral amyloid-β (Aβ) deposition in cognitively normal (CN) seniors on regional metabolism of specific brain regions known to be affected by p-tau deposition.
  
  
  
  Fluorodeoxyglucose positron emission tomography (FDG-PET), volumetric magnetic resonance imaging scans, and global amyloid standardized uptake value ratios (SUVr) were obtained for 210 CNs from the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI2). Region of interest (ROI) extraction was used to obtain functional SUVr from six bilateral ROIs: amygdala (AM), entorhinal cortex (EC), hippocampus, lateral orbitofrontal, posterior cingulate (PC), and middle temporal gyrus. Every metabolic SUVr set was averaged and analyzed against the corresponding subject's amyloid SUVr. Correlation analyses were conducted on the full group and between APOE ε4-positive and APOE ε4-negative subgroups.
  
  
  
  The APOE ε4+ group exhibited significantly higher metabolism in the EC (r = 0.270, P = .038) and AM (r = 0.267, P = .041). When a significance of the difference test was conducted between the APOE ε4+ and APOE ε4-groups, these same regions remained significant: P = .012 and P = .016, respectively. By contrast, the APOE ε4 group displayed only the conventionally expected result of reduced regional metabolism in the PC (r = -0.161, P = .048), with higher Aβ load.
  
  
  
  The effect of amyloid positivity on brain metabolism is regionally specific, and APOE ε4 status substantially modulates regional glucose uptake in these regions. The APOE ε4 allele may cause earlier emergence of clinical symptoms in AD via a mechanism that influences regional metabolic demand in specifically those regions where p-tau deposition is known to occur earliest.
authors.affiliation: Department of Neurology, Michigan State University, East Lansing, MI, USA; Department of Radiology, Michigan State University, East Lansing, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA. Electronic address: andrea.bozoki@ht.msu.edu.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Bozoki
authors.affiliation: Neuroscience Program, Michigan State University, East Lansing, MI, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Zdanukiewicz
authors.affiliation: Department of Radiology, Michigan State University, East Lansing, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA; Department of Psychology, Michigan State University, East Lansing, MI, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Zhu
mesh_terms: D000368:Aged; D000375:Aging; D000682:Amyloid / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: ADNI; APOE; Amyloid; FDG-PET; Florbetapir-PET