S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice

Andrea Fuso, Vincenzina Nicolia, Laura Ricceri, Rosaria A. Cavallaro, Elisa Isopi, Franco Mangia, Maria Teresa Fiorenza, Sigfrido Scarpa

Research output: Contribution to journalArticlepeer-review

Abstract

Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated. We previously demonstrated that hyperhomocysteinemia and DNA hypomethylation induced by B vitamin deficiency are associated with PSEN1 and BACE1 overexpression and amyloid production. The present study is aimed at assessing S-adenosylmethionine effects in mice kept under a condition of B vitamin deficiency. To this end, TgCRND8 mice and wild-type littermates were assigned to control or B vitamin deficient diet, with or without S-adenosylmethionine supplementation. We found that S-adenosylmethionine reduced amyloid production, increased spatial memory in TgCRND8 mice and inhibited the upregulation of B vitamin deficiency-induced PSEN1 and BACE1 expression and Tau phosphorylation in TgCRND8 and wild-type mice. Furthermore, S-adenosylmethionine treatment reduced plaque spreading independently on B vitamin deficiency. These results strengthen our previous observations on the possible role of one-carbon metabolism in Alzheimer's disease, highlighting hyperhomocysteinemia-related mechanisms in dementia onset/progression and encourage further studies aimed at evaluating the use of S-adenosylmethionine as a potential candidate drug for the treatment of the disease.

Original languageEnglish
JournalNeurobiology of Aging
Volume33
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Alzheimer's disease
  • Alzheimer's treatment
  • B vitamins
  • Homocysteine
  • One-carbon metabolism
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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