Alzheimer’s disease (AD) affects over 110,000 older adults in Wisconsin and remains without a cure. Emerging evidence suggests the gut microbiome may play a role in AD pathology, but how these changes unfold over time is not well understood. This project analyzed longitudinal fecal samples and fluid biomarkers from participants in the Wisconsin Registry for Alzheimer’s Prevention and the Alzheimer’s Disease Research Center. Results showed an increase in potentially pathogenic taxa alongside a decrease in beneficial microbes in amyloid-positive individuals compared to amyloid-negative individuals. This work contributes to understanding early biological processes that may influence later disease risk and has the potential to inform future prevention and intervention strategies.
The Challenge
Alzheimer’s disease is a progressive neurodegenerative disease that affects memory, thinking, and behavior. In Wisconsin, more than 110,000 older adults have Alzheimer’s disease. Many factors, including the gut microbiome, are suggested to contribute to the pathology of AD.
Project Goals
The goal of this project was to determine whether longitudinal changes in gut microbiome composition differ by amyloid status in Alzheimer’s disease, with the long-term objective of identifying early microbial signatures that may inform risk stratification, prevention strategies and future mechanistic studies.
Results
The research team completed longitudinal analyses of gut microbiome data from participants recruited through the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention. The study included unique participants with fecal samples collected at two time points. Amyloid positivity, commonly associated with Alzheimer’s disease, was determined using established imaging and fluid biomarker thresholds. Results demonstrated an increasing abundance of potentially pathogenic taxa alongside decreasing abundance of beneficial microbes in amyloid-positive individuals compared to amyloid-negative individuals. This suggests a pattern of progressive gut dysbiosis, or imbalance, associated with amyloid positivity. Next steps will include expanding analyses to additional cohorts and time points, integrating functional and metabolomic data and informing the design of microbiome-based intervention studies at earlier stages of Alzheimer’s disease.
