Epigenetic regulons in Alzheimer's disease

Alzheimer's disease is one of the most prevalent forms of dementia that occur genetically or sporadically (with increasing age) in the population of 65 years and above. The pathological hallmarks of AD include the formation of extracellular senile plaques of amyloid beta peptides 42 (Aβ42) and intracellular neurofibrillary tangles associated with hyperphosphorylated tau protein. AD has been reported as an outcome of multiple probabilistic factors such as age, lifestyle, oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and epigenetics. Epigenetics are heritable changes in gene expression that give a phenotype without altering the DNA sequences. Epigenetic mechanisms include DNA methylation, hydroxymethylation, histone modifications, regulation of miRNAs and long non-coding RNAs, which are reported to be dysregulated in AD. Further, epigenetic mechanisms have been shown as a key player as they regulate memory development, where DNA methylation and post-translational modifications of histone tails are the prime epigenetic markers. Also, alterations of AD-related genes cause pathogenesis on the transcriptional level. In the current chapter, we summarize the role of epigenetics in the onset and progression of AD and the use of epigenetic therapeutics to ameliorate the constraints of AD.