Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, and environmental factors are involved. Epigenetic factors have emerged as important mediators of aging, neurodegeneration, and brain disorders. Epigenomic changes underlying the phenotypic expression of AD, represented by deposits of extracellular Aβ aggregates in senile plaques, intracellular neurofibrillary tangles, neuronal loss, dendritic desarborization, and neurochemical alterations are candidate targets for therapeutic intervention. Changes in DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA dysregulation can affect AD-related gene expression, leading to the multistep process of premature neurodegeneration. Epigenetic modifications are reversible and can be potentially targeted by pharmacological and dietary interventions
