Cholinesterase inhibitor affects the amyloid precursor protein isoforms in patients with Alzheimer's disease.

An altered platelet ratio of amyloid precursor protein (APP) isoforms might be a diagnostic, predictive, or therapeutic marker for Alzheimer's disease (AD). Our purpose was to test the hypothesis that this ratio might serve as a therapeutic marker for AD patients treated with the cholinesterase inhibitor, galantamine. Thirty-nine patients (mean age 76.6 +/- 9.4 years) with AD were treated with galantamine for 12 weeks. Patients were evaluated at baseline, 4 and 12 weeks by cognitive testing along with a determination of their platelet APP isoform ratio. Western blotting was performed to calculate the APP isoform ratio. At the end of the treatment, cognitive scores significantly improved, and the ratio of the high-molecular-weight (130 kDa) isoform to the low-molecular-weight (110-106 kDa) isoforms increased. These results suggest that cholinesterase inhibition might be involved in APP processing.