MicroRNAs as Diagnostic Biomarkers for Alzheimer’s Disease and Related Dementias

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of late-life dementia. As pathology spreads through the brain, affected individuals experience devastating cognitive decline, linguistic impairments, mood changes, and behavioral issues. Developing effective disease-modifying therapies remains a persistent challenge because diagnosis typically occurs at a late stage, long after extensive, irreversible neuronal and synaptic loss has taken place. To overcome these diagnostic and therapeutic bottlenecks, attention has shifted to microRNAs (miRNAs), the most prominent class of abundant, small non-coding RNAs that post-transcriptionally regulate eukaryotic gene expression networks. This review delineates the critical functions of specific miRNAs in orchestrating the three primary pathological pillars of AD: amyloid-β (Aβ) buildup, chronic neuroinflammation, and systemic oxidative stress. Unraveling these complex epigenetic interactions contributes fundamentally to understanding AD’s pathology, offering highly sensitive avenues for early blood-based biomarker discovery and highlighting promising targets for innovative, RNA-targeted clinical therapeutics.