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-ε4 carriers and ε4 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-ε4 carriers displayed a higher increase compared to ε4 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.

ApoE genotype influences the biological effect of donepezil on APP metabolism in Alzheimer disease: Evidence from a peripheral model / B. Borroni, F. Colciaghi, L. Pastorino, S. Archetti, P. Corsini, F. Cattabeni, M.M.G. Di Luca, A. Padovani. - In: EUROPEAN NEUROPSYCHOPHARMACOLOGY. - ISSN 0924-977X. - 12:3(2002), pp. 195-200.

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

COLCIAGHI, FRANCESCA;F. Cattabeni;M.M.G. Di Luca;
2002

Abstract

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-ε4 carriers and ε4 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-ε4 carriers displayed a higher increase compared to ε4 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.
Alzheimer disease; Amyloid precursor protein (APP); Apolipoprotein E; Donepezil
Settore BIO/14 - Farmacologia
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/185042
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