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Related Experiment Video

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Public Health.

Warnakulasuriya Madb Fernando1,2, Ralph N Martins3,4,5,6,7,8,9,10,11,12, Stephanie R Rainey-Smith1,9,13,14,15,16,4,17,18

  • 1Edith Cowan University, Perth, Western Australia, Australia.

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|December 23, 2025
PubMed
Summary

Age, sex, and APOE ε4 status significantly impact gut microbiota and short-chain fatty acid (SCFA) production in preclinical Alzheimer's disease (AD). Older female APOE ε4 carriers show the most significant butyrate decline, suggesting gut health interventions may delay AD progression.

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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.