Effect of APOE ε4 genotype on amyloid--ß, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

Background and purpose: The presence of apolipoprotein E e4 (APOE e4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE e4 on amyloid--ss (A ss) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). Methods: We 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, 18F--florbetapir positron emission tomography (PET), and 18F-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24--month scans were included for follow--up study. Results: Voxelwise analysis revealed that APOE e4 carriers exhibited greater baseline A ss deposition than APOE e4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE e4 noncarriers and APOE e4 carriers in terms of 18F--FDG PET standardized uptake value ratio and GM volume. Region of interest--based analysis showed statistically significant greater A ss deposition in APOE e4 carriers than APOE e4 noncarriers only in aMCI patients. Furthermore, APOE e4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in A ss deposition than APOE e4 noncarriers in both diagnostic groups. Conclusions: Our findings suggest a differential effect of APOE e4 on A ss pathology, glucose metabolism, and GM volume. Studying APOE e4--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.