S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice.
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.
Department of Surgery P. Valdoni, Via Antonio Scarpa, 14-00161, Sapienza University of Rome, Italy. andrea.fuso@uniroma1.it
Andrea
A
Fuso
Vincenzina
V
Nicolia
Laura
L
Ricceri
Rosaria A
RA
Cavallaro
Elisa
E
Isopi
Franco
F
Mangia
Maria Teresa
MT
Fiorenza
Sigfrido
S
Scarpa
D000200:Action Potentials / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D018450:Disease Progression; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D014804:Vitamin B Deficiency / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D012436:S-Adenosylmethionine