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Basic Science and Pathogenesis.

Tehniat Faraz Ahmed1, Zeba Haque1, Affan Ahmed1

  • 1Dow University of Health Sciences, Karachi, Sindh, Pakistan.

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

This study identifies microRNAs linking insulin resistance (IR) and Alzheimer's disease (AD). These microRNAs may serve as early biomarkers for AD in patients with IR.

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Area of Science:

  • Biochemistry
  • Genetics
  • Neuroscience

Background:

  • Alzheimer's disease (AD) pathophysiology remains unclear, hindering treatment development.
  • Insulin resistance (IR), linked to diabetes and metabolic syndrome, shares risk factors with AD, but connecting mechanisms are unknown.
  • MicroRNAs are implicated in both IR and AD, yet no studies have identified those targeting both pathways.

Purpose of the Study:

  • To bioinformatically identify microRNAs simultaneously targeting IR and AD pathways.
  • To analyze the functional annotation of target genes to uncover shared regulatory mechanisms between IR and AD.

Main Methods:

  • Utilized five prediction tools and two experimental validation databases to identify microRNAs targeting key IR genes.
  • Performed KEGG analysis and constructed protein-protein interaction networks to identify microRNAs targeting AD genes.
  • Conducted functional annotation of target genes using DAVID to identify common Gene Ontology terms.

Main Results:

  • Identified microRNAs targeting 299 AD-related genes, with miR-16-5p targeting the most.
  • miR-7-5p, let-7a-5p, let-7b-5p, miR-15b-5p, miR-16-5p, miR-17-5p, and miR-424-5p ranked highest based on AD target scores.
  • Target genes were enriched in negative regulation of transcription, chromatin remodeling, and cell cycle control, with functions in protein binding and kinase activity.

Conclusions:

  • The identified microRNAs represent potential pathogenic links between AD and IR.
  • These microRNAs are recommended for further study as early biomarkers for AD in patients with IR.