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Basic Science and Pathogenesis.

Jingxian Chen1, Bin Jiao1, Lu Shen1

  • 1Xiangya Hospital, Central South University, Changsha, Hunan, China.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Moraxella catarrhalis bacteria and its outer membrane protein UspA1 are linked to Alzheimer's disease (AD) pathogenesis. This oral bacterium exacerbates AD symptoms by increasing amyloid precursor protein (APP) and amyloid-beta (Aβ) levels.

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Area of Science:

  • Neuroscience
  • Microbiology
  • Genetics

Background:

  • Alzheimer's disease (AD) pathogenesis is multifactorial, with hypotheses including amyloid-beta (Aβ) cascade, tau hyperphosphorylation, and inflammation.
  • The specific role of oral microbiota in AD development remains largely unexplored.

Purpose of the Study:

  • To investigate the association between oral microbiota, specifically Moraxella catarrhalis, and Alzheimer's disease.
  • To elucidate the mechanisms by which Moraxella catarrhalis may contribute to AD pathogenesis.

Main Methods:

  • 16S rDNA sequencing and qPCR were used to compare Moraxella species abundance in cerebrospinal fluid of AD patients and controls.
  • Cellular and animal models (5xFAD mice) were utilized to assess the impact of Moraxella catarrhalis, its extracellular vesicles, and UspA1 protein on amyloid precursor protein (APP) and Aβ levels.
  • Behavioral and pathological assessments were performed in mouse models.

Main Results:

  • Moraxella species were found in significantly higher abundance in AD patients.
  • Moraxella catarrhalis, its extracellular vesicles, and UspA1 protein overexpression upregulated APP and Aβ levels in vitro.
  • Intranasal Moraxella catarrhalis administration or hippocampal UspA1 overexpression in mice elevated brain APP and Aβ levels, worsening cognitive deficits.

Conclusions:

  • Moraxella catarrhalis contributes to AD pathogenesis via its extracellular vesicles and UspA1 protein.
  • These components interact with the APP proteolytic pathway, increasing Aβ generation.
  • The findings highlight a potential link between oral bacteria and Alzheimer's disease progression.