
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.09.13.24313582
preprint
1
Article
APOE4 and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer’s Pathology: New findings from the ADNI
Lathika Rajendrakumar Aravind http://orcid.org/0000-0002-4286-7265

Arbeev Konstantin G. http://orcid.org/0000-0002-4195-7832

Bagley Olivia
Yashin Anatoliy I.
Ukraintseva Svetlana
Alzheimer’s Disease Neuroimaging Initiative
14 9 2024
2024.09.13.24313582https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.09.13.24313582
nihpp-2024.09.13.24313582.pdf
Abstract

Introduction

We investigated the interplay between infections and APOE4 on brain glucose hypometabolism, an early preclinical feature of Alzheimer’s Disease (AD) pathology.

Methods

Multivariate 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 of APOE4 were evaluated.

Results

Infections were associated with greater hypometabolism [0.15, 95% CI: 0.03, 0.27, p=0.01], with a more pronounced effect among APOE4 carriers, indicating an interaction effect. A higher HCI (0.44, p=0.01) was observed in APOE4 carriers 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.

Conclusion

Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a “multi-hit” mechanism in AD development.
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