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Basic Science and Pathogenesis.

Printha Wijesinghe1, Jeanne Xi1, Matthew Campbell1

  • 1The University of British Columbia, Vancouver, BC, Canada.

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

Female mice show early Alzheimer's disease (AD) vulnerability with altered microRNAs (miRNAs) and gene expression. These sex-specific differences in AD pathogenesis lessen as the mice age.

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) disproportionately affects women.
  • Multifactorial elements contribute to AD sex disparities, including genetics and biology.
  • Investigating sex-specific microRNA (miRNA) roles in AD pathogenesis is crucial.

Purpose of the Study:

  • To examine sex-specific differences in miRNA expression in a mouse model of AD.
  • To identify miRNAs and associated genes involved in AD pathogenesis.
  • To understand the temporal changes in these molecular differences.

Main Methods:

  • Utilized 3xTg-AD mice and sibling controls of both sexes at 3, 6, and 12 months.
  • Screened 14 miRNAs and analyzed 32 genes in the neocortex-hippocampus.
  • Employed TaqMan Advanced miRNA assays and RT-qPCR for expression analysis.

Main Results:

  • Female mice at 3 months showed downregulated amyloidogenic miRNAs and differential gene expression.
  • APP and MAPT transgene expression varied by sex and age.
  • Upregulated inflammatory cytokines and downregulated neuroinflammatory markers were observed.

Conclusions:

  • Female 3xTg-AD mice exhibit early vulnerability at 3 months, with distinct miRNA and gene expression profiles.
  • These sex-specific molecular differences in AD pathogenesis decrease with age.