A plasma miRNA signature, including miR-495, as early diagnostic biomarkers associated with cognitive decline in Alzheimer's disease

Alzheimers Dement (Amst). 2025 Nov 2;17(4):e70213. doi: 10.1002/dad2.70213. eCollection 2025 Oct-Dec.

Abstract

Introduction: A definitive diagnosis of Alzheimer's disease (AD) requires the identification of pathological changes. Plasma miRNAs have emerged as potential AD diagnostic biomarkers.

Methods: A matched case-control study was conducted using convenience sampling to evaluate the ability of candidate miRNAs in differentiating probable AD patients with mild cognitive impairment (MCI) or mild dementia (MD) stages. The initial sample included 29 patients and 58 controls. Plasma levels of miRNAs were measured by real-time polymerase chain reaction (RT-PCR) and their associations with scores from a comprehensive neuropsychological battery of cognitive tests analyzed by Spearman's correlation.

Results: A miR-181a, miR-181c, and miR-495 signature showed area-under-curve values indicative of strong diagnostic capacity and biomarker-based staging. Higher levels of these miRNAs were associated with worse scores in the different assessed cognitive tests.

Discussion: This study reports for the first-time alterations in plasma miR-495 levels in both MCI and MD patients. Future studies with larger cohorts are essential to validate the findings.

Highlights: Alterations in plasma miR-495 levels are reported for the first time in AD patients.miR-181a, miR-181c, and miR-495 levels were higher in AD patients compared to controls.Higher levels of these miRNAs were related to worse cognitive test scores.miRNA signature was able to distinguish AD stages.

Keywords: Alzheimer's disease; cognitive domains; miRNAs; mild cognitive impairment; plasma biomarkers.