Work

Change in gut microbiome precedes symptomatic Alzheimer’s disease and is correlated with amyloid-beta accumulation in the brain

Year: 2026

Type: preprint

Abstract: ABSTRACT INTRODUCTION Alzheimer’s disease (AD) begins with cerebral amyloid-beta (AP) deposition decades before clinical symptoms. While the microbiota–gut–brain axis has been implicated in AD, its role in this preclinical phase remains unclear. We examined potential links between gut microbiome features and presymptomatic cerebral Ap burden. METHODS Asymptomatic individuals (n=101, median age 70.0 years, 53% female) underwent cognitive assessment, cerebral Ap quantification, and stool metagenomic sequencing. Associations between microbial characteristics and Ap levels were performed using multivariable-adjusted ordinal logistic regression. RESULTS Gut microbiota composition varied with Ap levels (p(perm)=0.03, R 2 =0.014). Higher Ap was associated with increased Alistipes communis, and decreased Anaerotignum faecicola and Eubacterium rectale, abundance (q<0.001). Ap-associated microbiome traits corresponded to lower biosynthetic capacity for y-aminobutyric acid, and systemic regulators of immunity and autophagy (q<0.01). DISCUSSION Early Ap accumulation is associated with distinct gut microbial signatures and reduced neuroactive metabolic potential, identifying targets for potential preclinical AD intervention.

Source: medRxiv

DOI: 10.64898/2026.10.15.26365677