TY - JOUR
T1 - S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice
AU - Fuso, Andrea
AU - Nicolia, Vincenzina
AU - Ricceri, Laura
AU - Cavallaro, Rosaria A.
AU - Isopi, Elisa
AU - Mangia, Franco
AU - Fiorenza, Maria Teresa
AU - Scarpa, Sigfrido
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Alzheimer's treatment
KW - B vitamins
KW - Homocysteine
KW - One-carbon metabolism
KW - S-adenosylmethionine
UR - http://www.scopus.com/inward/record.url?scp=84860368886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860368886&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2011.12.013
DO - 10.1016/j.neurobiolaging.2011.12.013
M3 - Article
C2 - 22221883
AN - SCOPUS:84860368886
VL - 33
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 7
ER -