TY - JOUR
T1 - The transmethylation cycle in the brain of Alzheimer patients
AU - Mulder, Cees
AU - Schoonenboom, Niki S.M.
AU - Jansen, Erwin E.W.
AU - Verhoeven, Nanda M.
AU - Van Kamp, Gerard J.
AU - Jakobs, Cornelis
AU - Scheltens, Philip
PY - 2005/9/30
Y1 - 2005/9/30
N2 - Homocysteine accumulation, frequently observed in plasma of AD patients, may be a sign of a reduced activity of the brain methionine-homocysteine transmethylation cycle. S-Adenosylmethionine (SAM) is the main methyl donor in several transmethylation reactions. The demethylated product of SAM, S-adenosylhomocysteine (SAH), is hydrolyzed to yield homocysteine, which can be remethylated to methionine by transfer of a methyl group of 5- methyltetrahydrofolate (5-MTHF). A reduced activity of the transmethylation cycle in the brain may result in hypomethylation of the promoter of the presenilin 1 (PS1) gene, which will lead to overexpression of presenilin 1 and, consequently, to increased Aβ1-42 (Aβ42) formation. Brain transmethylation was studied in 30 patients with 'probable' AD and 28 age-matched non-demented controls by measuring the cerebrospinal fluid (CSF) levels of SAM, SAH and 5-MTHF. 5-MTHF was determined by HPLC with electrochemical detection, while SAM and SAH were assayed by stable isotope dilution tandem mass spectrometry. We found no statistical differences between AD patients and controls for 5-MTHF, SAM and SAH levels, and the SAM/SAH-ratio in CSF. These findings argue against a possible change in methylation of the promoter and expression of PS1.
AB - Homocysteine accumulation, frequently observed in plasma of AD patients, may be a sign of a reduced activity of the brain methionine-homocysteine transmethylation cycle. S-Adenosylmethionine (SAM) is the main methyl donor in several transmethylation reactions. The demethylated product of SAM, S-adenosylhomocysteine (SAH), is hydrolyzed to yield homocysteine, which can be remethylated to methionine by transfer of a methyl group of 5- methyltetrahydrofolate (5-MTHF). A reduced activity of the transmethylation cycle in the brain may result in hypomethylation of the promoter of the presenilin 1 (PS1) gene, which will lead to overexpression of presenilin 1 and, consequently, to increased Aβ1-42 (Aβ42) formation. Brain transmethylation was studied in 30 patients with 'probable' AD and 28 age-matched non-demented controls by measuring the cerebrospinal fluid (CSF) levels of SAM, SAH and 5-MTHF. 5-MTHF was determined by HPLC with electrochemical detection, while SAM and SAH were assayed by stable isotope dilution tandem mass spectrometry. We found no statistical differences between AD patients and controls for 5-MTHF, SAM and SAH levels, and the SAM/SAH-ratio in CSF. These findings argue against a possible change in methylation of the promoter and expression of PS1.
UR - http://www.scopus.com/inward/record.url?scp=23044452934&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2005.03.073
DO - 10.1016/j.neulet.2005.03.073
M3 - Article
C2 - 16040194
AN - SCOPUS:23044452934
VL - 386
SP - 69
EP - 71
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -