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Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and

Scott E Counts1,2, John S Beck1, Bryan Maloney3

  • 1Department of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|February 26, 2025
PubMed
Abstract

Insights

This study reveals novel microRNA (miRNA) signatures in Alzheimer's disease (AD) and mild cognitive impairment (MCI), correlating with cognitive decline and brain pathology. These findings offer potential for precision medicine approaches in AD.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • MicroRNA (miRNA) activity is a critical regulator in Alzheimer's disease (AD) pathophysiology.
  • The specific roles of miRNAs in AD progression, resilience, and mild cognitive impairment (MCI) are not fully understood.

Purpose of the Study:

  • To investigate miRNA expression profiles in relation to AD, MCI, and resilience.
  • To identify miRNA-mRNA interactions and signaling pathways implicated in AD pathogenesis and risk.

Main Methods:

  • miRNA sequencing of post mortem posterior cingulate cortex (PCC) samples from individuals with no cognitive impairment (NCI), MCI, and AD.
  • Bioinformatic analyses including differential expression, target prediction, interactome modeling, functional enrichment, and AD risk modeling.

Main Results:

  • Distinct miRNA groups, mRNA targets, and signaling pathways were identified that differentiate AD, MCI, and resilient NCI individuals.
  • miRNAs correlated significantly with ante mortem cognitive performance and post mortem neuropathological burden.
  • Specific miRNAs were associated with AD risk, with age as a covariate.

Conclusions:

  • Dysregulated miRNAs are key features of AD and distinguish MCI and resilience.
  • Identified miRNA pathways involve insulin, prolactin, kinases, and neurite plasticity.
  • Harnessing miRNA activity presents a potential therapeutic strategy for AD, enabling precision medicine.
Keywords:
dementiamicroRNAmild cognitive impairmentnon‐coding RNAresilience

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