ArticleJournal of neurology2025
Altered gut microbiota mediates the association between APOE genotype and amyloid-β accumulation in middle-aged adults.
Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- The impact of APOE genotype, age, and sex on gut microbiota in a mouse model of Alzheimer's Disease: an exploration of their interactions.Biology of sex differences · 2026Article
- Association of Human Gut Microbiota with Alzheimer's Disease Pathogenesis: An Exploratory Clinical Study.Brain sciences · 2026Article
- Evaluating the gut microbiome, dietary patterns, and cognition: a sub-study protocol from the brain health and the gut microbiome study in cognitive decline (bMicrobiome study).Gut microbiome (Cambridge, England) · 2026Article
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Abstract
backgroundThe apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer's disease, yet the mechanisms linking APOE to amyloid-β (Aβ) pathology remain incompletely understood. Emerging evidence suggests that the gut microbiome may modulate neurodegeneration; however, its role as a mediator in the APOE-Aβ relationship remains unclear.
objectiveEvaluate whether specific microbial taxa mediate APOE-related effects on brain Aβ burden in a population-based study.
methodsThis study involved 227 participants from the Framingham Heart Study with stool 16S rRNA sequencing and carbon-11 Pittsburgh Compound-B imaging for Aβ collected at the third examination (2016-2019). Associations between gut microbiota and global/regional Aβ deposition were assessed using multivariable models. We stratified participants by APOE ε4 status and conducted mediation analysis to evaluate whether specific taxa mediated APOE-related effects on Aβ. Microbial functional potential was inferred to examine enrichment of metabolic pathways.
resultsHigher Aβ burden was significantly associated with the depletion of protective genera (e.g., Faecalibacterium, Ruminococcus, Butyricicoccus) and the enrichment of pro-inflammatory taxa (e.g., Alistipes, Bacteroides) and Barnesiella. These associations were more pronounced in APOE ε4 carriers, who exhibited a broader spectrum of microbial dysbiosis. Mediation analysis showed that Ruminococcus, Butyricicoccus, Clostridium, and Christensenellaceae collectively mediated ~ 0.3-0.4% of the effect of APOE ε4 on global Aβ burden. Functional profiling revealed a reduced abundance of microbial genes involved in key metabolic pathways among individuals with higher Aβ levels.
conclusionGut microbiome composition mediates the deleterious effect of APOE ε4 on cerebral amyloid deposition, suggesting that microbiome-targeted interventions may mitigate APOE-related risk.
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