Epigenetics of Alzheimer’s Disease: Past, Present and Future

Alzheimer’s disease (AD) exemplifies a looming epidemic lacking effective treatment and manifests with the accumulation of neurofibrillary tangles, amyloid-β plaques, neuroinflammation, behavioral changes, and acute cognitive impairments. It is a complex, multifactorial disorder that arises from the intricate interaction between environment and genetic factors, restrained via epigenetic machinery. Though the research progress has improved the understanding of clinical manifestations and disease advancement, the causal mechanism of detrimental consequences remains undefined. Despite the substantial improvement in recent diagnostic modalities, it is challenging to distinguish AD from other forms of dementia. Accurate diagnosis is a major glitch in AD as it banks on the symptoms and clinical criteria. Several studies are underway in exploring novel and reliable biomarkers for AD. In this direction, epigenetic alterations have transpired as key modulators in AD pathogenesis with the impeding inferences for the management of this neurological disorder. The present chapter aims to discuss the significance of epigenetic modifications reported in the pathophysiology of AD such as DNA methylation, hydroxy-methylation, methylation of mtDNA, histone modifications, and noncoding RNAs. Additionally, the chapter also describes the possible therapeutic avenues that target epigenetic modifications in AD. 

Keywords: Alzheimer’s disease, DNA methylation, Epigenetic therapy, Histone modifications, Non-coding RNAs.