Short-term treatment with rivastigmine and plasma levels of Abeta peptides in Alzheimer's disease.
Deregulation of APP metabolism is considered to be a key pathogenic event in Alzheimer's disease. Data from cell cultures indicate that the secretion of Abeta1-42 might be inhibited by cholinesterase inhibitors, possibly via M1 receptors stimulation. Treatment with tacrine, a dual acetyl- and butyrylcholinesterase inhibitor, had no significant effect on mean plasma Abeta species concentrations. However, a correlation was observed between higher drug concentrations and lower Abeta levels that might indicate an effect on APP metabolism with an increased alpha-cleavage. Abeta1-40 and Abeta1-42 levels were measured in the plasma of 28 AD subjects by means of a commercially available ELISA before rivastigmine treatment and at week 2 after the first dose of the drug (3 mg/day) had been administered. Treatment with rivastigmine exhibited a significant effect on mean plasma concentrations of Abeta1-42 (mean difference 7.8+/-8.4, t=-4.9, pmean difference 7.8+/-8.4, t=-4.9, p<0.001) with a negative correlation with the patients age (Pearson's R=-0.40, p=0.035). No significant effect on plasma Abeta1-40 was observed. The observed increase of mean levels of plasma Abeta1-42 after rivastigmine treatment might indicate an effect of the drug on Abeta metabolism, mobilization of Abeta1-42 from deposits in the affected brain areas and a consecutive Ab1-42 brain-to-plasma efflux. The negative correlation between Abeta1-42 plasma levels changes and age may be a sign of impairment of this process in the older patients. A large individual variation of the observed response, however, excludes drawing definite conclusions. Whether those subjects who respond to rivastigmine in terms of Abeta1-42 plasma levels changes also respond clinically needs to be established.
Sobow
Tomasz
T
Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Łódź, 8/10 Czechosłowacka St, 92-216 Łódź, Poland. tmsobow@csk.am.lodz.pl
Kloszewska
Iwona
I
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D048448:Phenylcarbamates / Q000627:therapeutic use*; D000068836:Rivastigmine; D013997:Time Factors
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine