DECREASED METHIONINE ADENOSYLTRANSFERASE ACTIVITY IN ERYTHROCYTES OF PATIENTS WITH DEMENTIA DISORDERS

ATP:l-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 (V-max and K-m 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 B-12 (B-12), the reduction in MAT K-m 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 B-12 (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 K-m for MAT. These findings support the hypothesis that aberrations in the B-12 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.