Epigenetics in neurodegeneration: emerging biomarkers and translational insights

Abstract

Neurodegenerative disorders (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are characterized by progressive neuronal loss leading to cognitive, motor, and behavioral impairments. Despite available interventions such as medications, physical therapy, and surgery, effective disease-modifying therapies remain elusive, with most treatments limited to symptom management. The multifactorial etiology of NDDs involves genetic, environmental, and increasingly recognized epigenetic factors that alter gene expression and drive disease onset and progression. Epigenetic mechanisms such as DNA methylation, histone modification, and chromatin remodeling play central roles in neuronal development, brain aging, and neurodegeneration. Recent advances highlight the potential of epigenetic biomarkers as diagnostic and prognostic tools, enabling early detection, monitoring of disease progression, and evaluation of therapeutic response. Protein- and microRNA-based biomarkers in biofluids, including blood and cerebrospinal fluid, provide promising insights into disease pathology and may support precision medicine approaches. This review explores current progress in identifying and validating epigenetic biomarkers and discusses their therapeutic implications, underscoring their transformative potential for improving diagnosis and treatment strategies in NDDs.