Genetic and Epigenetic Modifications in Alzheimer’s Disease: Pathophysiology, Biomarkers, and Therapeutics – A Systematic Review

Alzheimer’s disease (AD) is a complex neurodegenerative disorder marked by progressive cognitive decline, memory loss, and behavioral changes. While genetic factors such as mutations in APP , PSEN1 , PSEN2 , and the APOE ε 4 allele have been well established as risk factors, recent research highlights the role of epigenetic modifications in the disease’s pathophysiology. These modifications, including DNA methylation, histone acetylation, and microRNA regulation, influence gene expression without altering the DNA sequence, contributing to neuronal dysfunction and disease progression. This systematic review explores the interplay between genetic and epigenetic changes in AD, emphasizing their potential as biomarkers and therapeutic targets. Key genetic mutations and epigenetic alterations were found to modulate amyloid plaque formation, tau aggregation, and neuroinflammatory responses, all of which are critical in AD progression. Emerging therapeutic strategies, such as gene editing, stem cell therapy, and epigenetics-targeted drugs, offer promising avenues for modifying disease trajectories. Additionally, epigenetic biomarkers, like specific microRNAs and DNA methylation patterns, show potential for early diagnosis and disease monitoring. The findings highlight the need for future research to integrate genetic and epigenetic insights for personalized medicine approaches. Addressing ethical considerations in gene-editing technologies and long-term validation of epigenetic therapies remains essential for advancing AD treatment.