ArticlePloS one2025
APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.BMC neurology · 2026Article
- Unmasking the hidden catalyst: How infections trigger Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Review
- Lower hippocampal volume partly mediates the association between rs6859 in theFrontiers in aging neuroscience · 2026Article
- Lower Hippocampal Volume Partly Mediates the Association Between rs6859 in themedRxiv : the preprint server for health sciences · 2025Article
- Traffic-related air pollution significantly aggravates the detrimental effect of infections on the risk of Alzheimer's disease and other dementias, especially in non-carriers ofFrontiers in dementia · 2025Article
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Abstract
backgroundImpaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD.
methodsWe analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed.
resultsPrior infections were associated with greater HCI [β = 0.15, 95% CI: 0.03, 0.27, p = 0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p = 0.01) compared to 0.11 (p = 0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β = -0.01 (p = 0.02) and β = -0.01 (p = 0.04), respectively.
conclusionOur 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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