DNA methylation in the pathology of Alzheimer's disease: from gene to cognition

Abstract

Alzheimer's disease (AD) is a debilitating disorder that manifests with amyloid beta plaque deposition, neurofibrillary tangles, neuronal loss, and severe cognitive impairment. Although much effort has been made to decipher the pathogenesis of this disease, the mechanisms causing these detrimental outcomes remain obscure. Over the past few decades, neuroepigenetics has emerged as an important field that, among other things, explores how reversible modifications can change gene expression to control behavior and cognitive abilities. Among epigenetic modifications, DNA methylation requires further elucidation for the conflicting observations from AD research and its pivotal role in learning and memory. In this review, we focus on the essential components of DNA methylation, the effects of aberrant methylation on gene expressions in the amyloidogenic pathway and neurochemical processes, as well as memory epigenetics in Alzheimer's disease.

Neuroprotective Epigenetic Changes Induced by Maternal Treatment with an Inhibitor of Soluble Epoxide Hydrolase Prevents Early Alzheimer′s Disease Neurodegeneration

“…Epigenetic methylation of DNA silences gene expression by direct methylation of the cytosine carbon ring in the dinucleotide CpG repeats [ 29 ]. Impaired global DNA methylation has been associated with AD neuropathology and cognitive loss [ 30 ].…”

A novel cervix carcinoma biomarker: Pathological-epigenomics, integrated analysis of MethylMix algorithm and pathology for predicting response to cancer immunotherapy

“…In normal cells, a significant degree of methylation is characteristic of extragenic DNA (cytosines within CG dinucleotides) ( 36 ). Changes in methylation patterns, which may emerge with the age of the organism and cancer development, have been observed in three regions of exon 5 of the p53 gene in non-small cell lung cancer ( 36 , 37 ). With the application of real-time PCR technology (using primers for methylated and unmethylated sequences), we have been able to find new markers for early detection of cancer.…”

Decreased MEF2A Expression Regulated by Its Enhancer Methylation Inhibits Autophagy and May Play an Important Role in the Progression of Alzheimer’s Disease

“… Wu et al (2008) assessed AD-related gene methylation in peripheral blood leucocytes of diagnosed AD, which revealed decreased DNA methylation at the amyloid precursor protein (APP) promoter regions accompanied by upregulated APP transcripts. The methylation of other genes, including BACE1, PSEN1, SORL1, and NEP, involved in amyloidogenic pathway, was also shown to be related to AD ( Poon et al, 2020 ). The epigenetic mechanisms, including the methylation of GSK3β, BDNF, ANK1, BIN1, and RELN, have been consistently reported to play critical roles in neurochemical processes including long-term potentiation (LTP) and synaptic plasticity ( Jager et al, 2014 ; Poon et al, 2020 ).…”

“…The methylation of other genes, including BACE1, PSEN1, SORL1, and NEP, involved in amyloidogenic pathway, was also shown to be related to AD ( Poon et al, 2020 ). The epigenetic mechanisms, including the methylation of GSK3β, BDNF, ANK1, BIN1, and RELN, have been consistently reported to play critical roles in neurochemical processes including long-term potentiation (LTP) and synaptic plasticity ( Jager et al, 2014 ; Poon et al, 2020 ). We found that the MEF2A in AD had significantly higher levels of methylation in the SE region than in healthy controls.…”