Gut microbiome compositional and functional features associate with Alzheimer's disease pathology

Area of Science:

• Neuroscience
• Microbiology
• Genetics

Background:

• The gut microbiome's role in Alzheimer's disease (AD) is a growing area of research, but its specific composition and functional impact on AD pathology remain unclear.
• Understanding the gut microbiome offers a potential avenue for modifying Alzheimer's disease risk.

Purpose of the Study:

• To investigate the differences in gut microbiome composition and function between individuals with and without Alzheimer's disease (AD) dementia.
• To explore the association between gut microbiome features and cerebrospinal fluid (CSF) biomarkers related to AD pathology.

Main Methods:

• Shallow-shotgun metagenomics was employed to analyze fecal microbiome samples from participants in the Wisconsin Microbiome in Alzheimer's Risk Study.
• Differential abundance and ordinary least squares regression analyses were conducted to identify microbial features associated with AD and related pathologies.

Main Results:

• Significant differences in gut microbiome composition and function were observed between individuals with AD dementia and cognitively unimpaired (CU) individuals.
• These compositional differences were validated in an independent cohort, strengthening the findings.
• Specific gut microbiome features demonstrated differential abundance across various AD-related groups, including amyloid and APOE ε4 status.

Conclusions:

• The study confirms distinct gut microbiome profiles in individuals with AD dementia compared to CU individuals.
• Alterations in gut microbial composition and function are significantly correlated with CSF biomarkers of AD and related pathologies.
• These findings highlight a compelling link between the gut microbiome and the pathological processes underlying Alzheimer's disease.