Title : Epigenetic insights into alzheimer's disease: The critical role of DNA methylation
Abstract:
Alzheimer’s Disease (AD), a prevalent neurodegenerative disorder and the leading cause of dementia, is characterised by progressive memory loss and cognitive decline. Although the exact aetiology of AD remains unclear, recent research highlights the pivotal role of epigenetic modifications, particularly DNA methylation, in its pathogenesis. DNA methylation, the addition of methyl groups to cytosine residues typically within CpG islands, modulates gene expression without altering the DNA sequence and can either repress or activate genes critical for neuronal function. This review critically explores the complex and sometimes contradictory evidence regarding the influence of gene-specific DNA methylation on AD development. Focus is placed on the hypermethylation-induced suppression of neuroprotective genes such as Brain-Derived Neurotrophic Factor (BDNF) and Dual Specificity Phosphatase 22 (DUSP22), whose downregulation is linked to hallmark AD pathologies including tau hyperphosphorylation and synaptic dysfunction. Conversely, this review also addresses studies questioning a direct causal relationship between DNA methylation changes and AD, emphasizing the confounding effects of aging, environmental stressors, and individual variability. Therapeutically, the potential of DNA methyltransferase inhibitors to reverse aberrant methylation and restore neuroprotective gene expression is discussed, alongside the challenges of specificity, safety, and effective brain delivery. Emerging strategies such as precision epigenetic profiling and combination therapies targeting multiple pathological pathways hold promise for future AD treatment. Ultimately, a holistic understanding of genetic, epigenetic, and environmental interplay is essential to develop effective interventions that may slow or prevent AD progression, improving patient outcomes and quality of life.
