MicroRNAs as Potential Biomarkers for Alzheimer's Disease in Women

Abstract

Alzheimer's disease (AD) affects approximately 50 million people worldwide, with women comprising two-thirds of those affected. Despite this disproportionate impact, the sex-specific pathological mechanisms underlying AD in women remain poorly understood, and female-specific biomarkers have been significantly understudied. This critical knowledge gap requires focused research to improve diagnostic and therapeutic approaches for women with AD. In this review, we systematically examine the pathological mechanisms underlying AD in women, including sex-related differences in inflammation, autophagy, and metabolic dysfunction. We further explore microRNA (miRNA) expression patterns and evaluate miRNA candidates as potential biomarkers for AD in women based on current literature. Through this analysis, we identified approximately 20 miRNA candidates derived from diverse human samples, including brain tissue, blood, and cerebrospinal fluid, in multiple independent studies. These candidates demonstrate the potential for developing accessible, non-invasive biomarkers, particularly those identified in blood and cerebrospinal fluid. However, the limited overlap between studies highlights that female-specific miRNA biomarker research for AD remains in its early discovery phase, emphasizing the urgent need for large-scale validation studies and standardized methodological approaches to advance this promising field for clinical application.

Keywords: Alzheimer’s disease; biomarkers; female specific mechanism; inflammation; miRNAs; sex differences.

Figure 1

Gender Differences in Inflammation Pathways in AD. All abbreviations used in the diagram include: AD (Alzheimer’s disease), FOXP3 (Forkhead box P3), IL2RG (Interleukin 2 receptor subunit gamma), TLR7 (Toll-like receptor 7), IL-1β (Interleukin 1 beta), TNF-ά (Tumor necrosis factor-alpha), NOS (Nitric oxide synthase), NF-κB (Nuclear factor kappa B subunit 1), APOE4 (Apolipoprotein E 4), and BIN1 (Bridging integrator 1).