The impact of genetics and epigenetic factors on the development of Alzheimer's

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia in the elderly, accounting for approximately 60 to 70% of cases. It is characterized by progressive loss of memory, language and executive functions, progressing to total dependence and death. Increased life expectancy has increased the prevalence of AD, making it a growing challenge for health systems. Its pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles, leading to synaptic dysfunction and brain atrophy, aggravated by inflammation and oxidative stress. Although the etiology of AD is multifactorial, there is increasing evidence of the role of genetics and epigenetics in its pathogenesis. Mutations in the APP, PSEN1, PSEN2 genes and variants of the APOE gene, especially the ε4 isoform, have been widely associated with the risk of the disease. In parallel, epigenetic mechanisms, such as DNA methylation, histone modifications, and microRNAs, affect gene expression and are implicated in neurodegeneration, being influenced by environmental and lifestyle factors. This study consists of an exploratory, qualitative, and cross-sectional literature review. Nineteen articles published between 2020 and 2025, selected from the PubMed, SciELO, BVS, and MEDLINE databases, were analyzed, following the PRISMA guidelines. The analysis sought to understand how genetic and epigenetic factors contribute to the development and progression of AD, focusing on potential biomarkers, molecular pathways, and emerging therapeutic strategies. The discussion highlights that both genetic inheritance and epigenetic modifications interact in a complex way, modulating individual susceptibility to AD. Understanding these relationships is essential to advance early diagnosis and the development of personalized therapies, expanding the possibilities of prevention and clinical intervention.