Public Health

Area of Science:

• Microbiome research
• Neurodegenerative disease mechanisms
• Gut-brain axis

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
• Gut microbiota composition shifts may influence AD pathogenesis via gut-brain interactions.
• Preclinical AD stages are critical for understanding early disease pathways.

Purpose of the Study:

• Investigate the impact of age, sex, and APOE ε4 genotype on gut probiotic composition.
• Analyze microbial metabolite production, specifically short-chain fatty acids (SCFAs).
• Understand gut-brain axis alterations in cognitively unimpaired individuals at risk for AD.

Main Methods:

• Analysis of stool samples from 123 participants in the Australian Imaging Biomarkers and Lifestyle (AIBL) and WA Memory Study (WAMS).
• Metagenomic sequencing to assess gut microbial composition, focusing on Bifidobacterium and Lactobacillus.
• Gas-liquid chromatography to measure SCFAs like butyrate, propionate, and acetate.

Main Results:

• Older individuals (≥70 years) exhibited reduced microbial diversity with declines in Bacteroidetes and Firmicutes.
• Females showed lower Firmicutes, leading to reduced butyrate production.
• Older APOE ε4 carriers had decreased butyrate and increased acetate, with significant reductions in Bifidobacterium and Lactobacillus.

Conclusions:

• Age, sex, and APOE ε4 status significantly influence gut microbiota and SCFA profiles in preclinical AD.
• Reduced butyrate, especially in older female APOE ε4 carriers, indicates heightened vulnerability to dysbiosis and inflammation.
• Targeted probiotic interventions may restore gut balance and potentially delay AD progression.