Keywords
gene therapy
epigenetics
tau proteins
amyloid-beta
How to Cite
Abstract
Late-onset Alzheimer’s Disease (LOAD) represents a growing global health crisis, characterized by a complex interplay between genetic predisposition and environmental influences. While traditional therapeutic efforts have largely targeted amyloid-β and tau proteopathy with limited clinical success, attention has shifted toward the "epigenetic landscape" as a primary driver of neurodegeneration. This review explores the multifaceted roles of epigenetic mechanisms—including DNA methylation, histone modifications (acetylation and methylation), and non-coding RNA (miRNA, lncRNA, and circRNA) regulation—in the molecular pathogenesis of LOAD. We synthesize recent evidence demonstrating how dysregulation of these mechanisms leads to synaptic dysfunction, neuroinflammation, and impaired cognitive resilience. Furthermore, this review evaluates the emerging frontier of gene therapy and epigenome editing as transformative therapeutic strategies. We discuss the application of Adeno-Associated Virus (AAV) and lentiviral vectors in delivering neurotrophic factors and the potential of CRISPR/Cas9-based systems for precise modulation of risk genes like APOE4 and BACE1. Despite the promise of these biotechnological advances, significant translational challenges remain, including blood-brain barrier permeability, off-target effects, and the necessity for long-term safety profiles in an aging population. By integrating current knowledge of epigenetic shifts with the latest innovations in gene delivery, this review outlines a roadmap for precision medicine in Alzheimer’s therapy, emphasizing the transition from broad-spectrum interventions to targeted molecular modulation.
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