Decreased methionine adenosyltransferase activity in erythrocytes of patients with dementia disorders.
ATP:1-methionine S-adenosyltransferase (EC 2.5.1.6, MAT) activity was analyzed in erythrocytes from nine patients with a clinical diagnosis of probable Alzheimer's disease (Pro.AD), four with possible Alzheimer's disease (Pos.AD), three with mild cognitive dysfunction (MCD) and two with dementia of vascular origin (VD), and 10 age-matched control subjects. Significantly lower kinetic parameters (Vmax and Km towards methionine) for MAT were observed in all the dementia cases. In the subgroup of Pro.AD patients who also had low plasma levels of vitamin B12 (B12), the reduction in MAT Km was significantly correlated with an increase in the serum levels of homocysteine, while no such correlation was observed in all the other dementia groups. Treatment for 6 months of this subgroup of Pro.AD patients with B12 (1 mg x 7 days + 1 mg/week, i.m.), S-adenosylmethionine (SAM, 200 mg twice daily, p.o.) and folate (2.5 mg every 2 days, p.o.) caused a significant decrease in homocysteine in parallel with a significant increase in Km for MAT. These findings support the hypothesis that aberrations in the B12 dependent transmethylation reactions might be involved in the pathogenesis of dementia, and suggest that the evaluation of erythrocyte MAT activity may be a useful marker for the detection of such an aberration.
Gomes Trolin
C
C
Department of Medical Pharmacology, University of Uppsala, Sweden.
Regland
B
B
Oreland
L
L
D017677:Age Distribution; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology; D003704:Dementia / Q000201:enzymology*; D015140:Dementia, Vascular / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism*; D008875:Middle Aged
D008716:Methionine Adenosyltransferase