ApoE genotype influences the biological effect of donepezil on APP metabolism in Alzheimer disease: evidence from a peripheral model

Three major amyloid precursor protein (APP) forms with apparent molecular A eight ranging from 106 to 130 kDa are present in human platelets. Alzheimer disease (AD) is associated with a decreased APP forms ratio (APPr) between the three major forms. A total of 25 mild to moderate AD patients were investigated. Platelet APPr was studied before and after 30 days of acetylcholinesterase-inhibitor ;treatment (donepezil, 5 mg daily). Patients were grouped into non-is an element of4 carriers and is an element of4 carriers according to apolipoprotein E (ApOE) genotype. At baseline. all patients showed low APPr levels and no significant difference was found between the two ApoE subgroups. After treatment. although a marked improvement in APPr was observed in most patients. non-is an element of4 carriers displayed a higher increase compared to is an element of4 carriers (P<0.0001). The present study provides evidence that donepezil influences APP metabolism in platelets, and suggests that ApoE genotype might be an important modulating factor for drug responsiveness in AD. (C) 2002 Elsevier Science B.V. All rights reserved.