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Basic Science and Pathogenesis.

Kamada Lwere1

  • 1Makerere University, Kampala, Uganda, Uganda.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary

Gut microbiome shifts are linked to Alzheimer's disease (AD) and mild cognitive impairment (MCI) in Uganda. These findings highlight the gut-brain axis in neurodegeneration and suggest potential for early AD detection via microbiome analysis.

Area of Science:

  • Neuroscience
  • Microbiology
  • Genetics

Background:

  • Alzheimer's disease (AD) is a leading cause of cognitive decline globally.
  • Mechanisms of AD are poorly understood in sub-Saharan Africa (SSA) due to unique genetic, dietary, and environmental factors.
  • The gut microbiota is increasingly implicated in AD pathogenesis via neuroinflammation and gut-brain axis dysfunction.

Purpose of the Study:

  • To investigate phylogenetic and compositional shifts in the gut microbiome of individuals with AD, Mild Cognitive Impairment (MCI), and healthy controls in Uganda.
  • To provide insights into microbial dysbiosis and its association with cognitive decline in a low-resource setting.
  • To explore the gut microbiome's role in neurodegeneration within the SSA context.

Main Methods:

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  • Cross-sectional study analyzing stool samples from 104 participants (77 AD, 14 MCI, 13 controls).
  • 16S rRNA sequencing (V3-V4 region) and DADA2 for amplicon sequence variant (ASV) generation.
  • Beta diversity analysis using Weighted UniFrac and Bray-Curtis metrics, visualized with Principal Coordinate Analysis (PCoA) and statistically tested with PERMANOVA.

    • Main Results:

    • Distinct microbial shifts were observed across AD, MCI, and control groups, correlating with cognitive decline.
    • Weighted UniFrac PCoA showed clear clustering, with Axis 1 separating AD from controls (39.46% variation).
    • PERMANOVA confirmed significant group differences (Weighted UniFrac: R² = 0.18, p = 0.001; Bray-Curtis: R² = 0.21, p = 0.001), with MCI showing an intermediate profile.

    Conclusions:

    • Significant alterations in the gut microbiome are associated with Alzheimer's disease and mild cognitive impairment.
    • The transitional microbial profile in MCI suggests its potential as an early indicator of dysbiosis.
    • These findings support the development of microbiome-targeted strategies for early AD detection and intervention.