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Basic Science and Pathogenesis
Aiym Kaiyrlykyzy1,2, Gulnaz Zholdasbekova3, Dinara Alzhanova4
1Al-Farabi Kazakh National University, Almaty, Kazakhstan.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
Summary
This study in Kazakhstan identified smoking, dyslipidemia, and specific gut bacteria as risk factors for Alzheimer's disease (AD). Genetic links and elevated inflammatory markers highlight the disease's complexity and need for personalized approaches.
Area of Science:
- Neuroscience
- Genetics
- Microbiology
Background:
- Alzheimer's disease (AD) is a major cause of dementia with complex, multifactorial origins.
- Understanding risk factors across diverse populations is crucial for effective AD research and management.
Purpose of the Study:
- To investigate clinical, genetic, and microbial risk factors associated with Alzheimer's disease (AD) in a Kazakhstani cohort.
- To explore the interplay between host genetics, gut microbiome, and neuroinflammation in AD pathogenesis.
Main Methods:
- Analysis of 181 AD patients and 244 controls from Kazakhstan.
- Clinical assessment, genetic analysis (SNPs), gut microbiome profiling (16S rRNA sequencing), and serum cytokine/adiponectin measurements.
Main Results:
- Key dementia-associated variables included smoking, depression, dyslipidemia, insulin resistance, and liver dysfunction.
- Significant genetic findings include APOE, TOMM40, and MED12L SNPs, with APOE4 increasing AD risk by 1.9x.
- Alterations in gut microbiome (decreased Firmicutes/Bacteroidetes ratio, reduced Bifidobacterium) and elevated pro-inflammatory cytokines (IFN-γ, IL-6, TNF-β) were observed in AD patients.
Conclusions:
- Bio-geographic and environmental factors significantly influence AD risk and presentation.
- Findings suggest a complex interplay between host genetics, gut microbiota, and systemic inflammation in AD.
- Results support the development of personalized AD management strategies tailored to specific populations.
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