In recent years, in parallel with the growing awareness of the multifactorial nature of Late Onset Alzheimer’s
Disease, the possibility that epigenetic mechanisms could be involved in the onset and/or progression of the pathology assumed
an increasingly intriguing and leading role in Alzheimer’s research. Today, many scientific reports indicate the existence
of an epigenetic drift during ageing, in particular in Alzheimer’s subjects. At the same time, experimental evidences
are provided with the aim to demonstrate the causative or consequential role of epigenetic mechanisms. Our research
group was involved in the last ten years in studying DNA methylation, the main epigenetic modification, in relationship
to altered one-carbon metabolism (namely high homocysteine and low B vitamins levels), in Alzheimer’s experimental
models. Our previous findings about the demethylation of Presenilin1 gene promoter in nutritionally-induced
hyperhomocysteinemia in a transgenic mouse model clearly demonstrated that Presenilin1 is regulated by DNA methylation.
One of the open questions raised by our studies was if the observed demethylation was solely due to the induced imbalance
of one-carbon metabolism or could be a response to the massive deposition of amyloid plaques in transgenic
mice. Here we analyzed old (10 months) mice under standard diet in order to evidence possible changes in Presenilin1
promoter methylation in transgenic (TgCRND8 mice, carrying a double-mutated human APP transgene) vs. wt mice
(129Sv) after prolonged exposure to amyloid. We found no differences in Presenilin1 methylation despite a slight increase
in gene expression; these results suggest that amyloid production is not responsible for Presenilin1 demethylation in
TgCRND8 mice brain.