Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease?

Presenilin 1 (PS1) is a key factor for beta-amyloid (Ab) formation in Alzheimer disease (AD). Homocysteine accumulation, frequently observed in AD patients, may be a sign of a metabolic alteration in the S-adenosylmethionine (SAM) cycle, which generates the overexpression of genes controlled by methylation of their promoters, when the cytosine in CpG moieties becomes unmethylated. The methylation of a gene involved in the processing of amyloid precursor protein may prevent Ab formation by silencing the gene. Here we report that SAM administration, in human neuroblastoma SK-N-SH cell cultures, downregulates PS1 gene expression and Ab production.