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 weight 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-epsilon4 carriers and epsilon4 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-epsilon4 carriers displayed a higher increase compared to epsilon4 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.
Borroni
Barbara
B
Department of Neurology, University of Brescia, Piazzale Spediale Civili 1, 25123 Brescia, Italy.
Colciaghi
Francesca
F
Pastorino
Lucia
L
Archetti
Silvana
S
Corsini
Paola
P
Cattabeni
Flaminio
F
Di Luca
Monica
M
Padovani
Alessandro
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D005838:Genotype; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D012044:Regression Analysis
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil