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Conference presentation
The Gut‐Brain Connection: How Age, Sex, and APOE ε4 Influence Probiotic Balance in Early Alzheimer's Disease
Alzheimer's & dementia, Vol.21(Suppl. 6 (Public Health)), e096704
Wiley Periodicals LLC on behalf of Alzheimer's Association.
Alzheimer's Association International Conference® (Toronto, Canada/Online, 27/07/2025–31/07/2025)
2025
Abstract
Background
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with evidence suggesting gut microbiota plays a critical role in its onset and progression. Shifts in probiotic communities during the preclinical phase may influence disease pathways through gut‐brain interactions. This study investigates how age, sex, and APOE ε4 genotype impact probiotic composition and microbial metabolite production in cognitively unimpaired individuals.
Method
Stool samples from 123 participants in the Australian Imaging Biomarkers and Lifestyle (AIBL) study and WA Memory Study (WAMS) were analysed. Participants were grouped by age (<70, ≥70 years), sex, and APOE ε4 carrier status. Metagenomic sequencing assessed gut microbial composition, focusing on probiotics like Bifidobacterium and Lactobacillus. Gas‐liquid chromatography measured short‐chain fatty acids (SCFAs), including butyrate, propionate, and acetate.
Result
Gut Microbiota Composition: Dominant bacterial phyla included Actinobacteria, Bacteroidetes, Cyanobacteria, and Firmicutes across all groups. Age‐Related Changes: Older participants (≥70 years) showed significant declines in Bacteroidetes and Firmicutes, reflecting reduced microbial diversity. Sex‐Specific Differences: Females had lower Firmicutes levels, reducing butyrate production, essential for inflammation control and brain health. APOE ε4 Carriers: Older APOE ε4 carriers showed a decline in butyrate‐producing bacteria, particularly Faecalibacterium prausnitzii, leading to reduced butyrate and elevated acetate levels. Sex and APOE ε4: Female APOE ε4 carriers ≥70 exhibited the most pronounced butyrate decline, indicating increased vulnerability to dysbiosis and inflammation. Probiotic Alterations: Key probiotics, including Bifidobacterium and Lactobacillus, were significantly reduced in older APOE ε4 carriers.
Conclusion
Age, sex, and APOE ε4 status significantly influence gut microbiota composition and SCFA production at the preclinical stage of AD. Reduced butyrate levels, particularly in older female APOE ε4 carriers, highlight the importance of gut health in mitigating AD risk. These findings suggest targeted probiotic interventions could restore gut balance and delay AD progression.
Details
- Title
- The Gut‐Brain Connection: How Age, Sex, and APOE ε4 Influence Probiotic Balance in Early Alzheimer's Disease
- Authors/Creators
- Warnakulasuriya MADB Fernando - Australian Alzheimer's Research Foundation, Perth, Western Australia, AustraliaRalph N Martins - Macquarie UniversityStephanie R Rainey-Smith - Murdoch University, Centre for Healthy AgeingHamid R Sohrabi - Murdoch University, Centre for Healthy AgeingSamantha Ramachandra - Edith Cowan UniversitySithara Udeshini Dissanayaka - Edith Cowan University
- Publication Details
- Alzheimer's & dementia, Vol.21(Suppl. 6 (Public Health)), e096704
- Conference
- Alzheimer's Association International Conference® (Toronto, Canada/Online, 27/07/2025–31/07/2025)
- Publisher
- Wiley Periodicals LLC on behalf of Alzheimer's Association.
- Number of pages
- 2
- Identifiers
- 991005845958307891
- Copyright
- © 2025 The Alzheimer's Association.
- Murdoch Affiliation
- School of Psychology; Centre for Healthy Ageing; Health Futures Institute
- Language
- English
- Resource Type
- Conference presentation
- Note
- Abstract Only
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