Epigenetic factors in late-onset alzheimer’s disease: MTHFR and CTH gene polymorphisms, metabolic transsulfuration and methylation pathways, and B vitamins

Abstract

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia—a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B 12 (methylcobalamin), vitamin B 9 (folic acid), vitamin B 6 (pyridoxine), and SAM to patients in early stages of LOAD.