European Journal of Nutrition   2016 年 55 卷 5 期

2016.08.01

Purpose: Alzheimer???s disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid ?? (A??) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models. Methods: Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24??h with a combination of folic acid and either A?? oligomers or vehicle and were then incubated for 72??h with various concentrations of folic acid. AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with various doses of folic acid (0 or 600????g/kg). DNA methyltransferase (DNMT) activity, cell viability, methylation potential of cells, APP and PS1 expression, and the methylation of the respective promoters were determined. Results: A?? oligomers lowered DNMT activity, increased PS1 and APP expression, and decreased cell viability. Folic acid dose-dependently stimulated methylation potential and DNMT activity, altered PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially preserved cell viability. Folic acid increased PS1 and APP promoter methylation in AD transgenic mice. Conclusion: These results suggest a mechanism by which folic acid may prevent A?? oligomer-induced neuronal toxicity.