APOE4and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer’s Pathology: New Findings from the ADNI

Abstract

IntroductionWe investigated the interplay between infections andAPOE4on brain glucose hypometabolism, an early preclinical feature of Alzheimer’s Disease (AD) pathology.MethodsMultivariate linear regression analysis was performed on 1,509 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The outcomes were the rank-normalized hypometabolic convergence index (HCI) and statistical regions of interest (SROI) for AD and mild cognitive impairment (MCI). Further, the HCI and its change in the presence and absence ofAPOE4were evaluated.ResultsInfections were associated with greater hypometabolism [0.15, 95% CI: 0.03, 0.27, p=0.01], with a more pronounced effect amongAPOE4carriers, indicating an interaction effect. A higher HCI (0.44, p=0.01) was observed inAPOE4carriers with multiple infections, compared to (0.11, p=0.08) for those with a single infection, revealing a dose-response relationship. The corresponding estimates for the association of infections with SROI AD and SROI MCI were -0.01 (p=0.02) and -0.01 (p=0.04) respectively.ConclusionOur findings suggest that infections andAPOE4jointly contribute to brain glucose hypometabolism and AD pathology, supporting a “multi-hit” mechanism in AD development.