Background and purposeThe presence of apolipoprotein E epsilon 4 (APOE epsilon 4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE epsilon 4 on amyloid-beta (A beta) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI).MethodsWe included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1-weighted magnetic resonance imaging, F-18-florbetapir positron emission tomography (PET), and F-18-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24-month scans were included for follow-up study.ResultsVoxelwise analysis revealed that APOE epsilon 4 carriers exhibited greater baseline A beta deposition than APOE epsilon 4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE epsilon 4 noncarriers and APOE epsilon 4 carriers in terms of F-18-FDG PET standardized uptake value ratio and GM volume. Region of interest-based analysis showed statistically significant greater A beta deposition in APOE epsilon 4 carriers than APOE epsilon 4 noncarriers only in aMCI patients. Furthermore, APOE epsilon 4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in A beta deposition than APOE epsilon 4 noncarriers in both diagnostic groups.ConclusionsOur findings suggest a differential effect of APOE epsilon 4 on A beta pathology, glucose metabolism, and GM volume. Studying APOE epsilon 4-related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.