Amyloid precursor protein in platelets of patients with Alzheimer disease - Effect of acetylcholinesterase inhibitor treatment

Background: Amyloid precursor protein (APP) forms with apparent molecular w eights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets. Objective: To investigate whether acetylcholinesterase (AChE) inhibitor tre atment modifies the ratio of platelet APP forms in patients with AD. Patients and Methods: From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical e valuation including the Mini-Mental State Examination (MMSE) and platelet A PP forms analysis at baseline and after 30 days. During this interval, 20 o f 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjec ted to Western blot analysis using monoclonal antibody (22C11). The ratio b etween the immunoreactivity of the higher-molecular-weight APP form (130 kd ) and the lower forms (106 and 110 kd) was measured. Results: All patients taking donepezil completed the 30 days of treatment w ithout adverse effects. The platelet APP forms ratio at baseline did not di ffer between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant differ ence was found at follow-up (mean +/- SD optical density ratio: untreated A D, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improve ment in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P=.09). Conclusions: Administration of AChE inhibitors increases the ratio of APP f orms in platelets of patients with AD, suggesting a potential effect of ACh E inhibitors on APP trafficking or processing in a peripheral cell.