Defective phorbol ester-stimulated secretion of β-amyloid precursor protein from Alzheimer's disease fibroblasts

The present study shows that cultured fbroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduced response at low concentrations of phorbol-12,13-dibutyrate, with an EC 50 twofold higher than control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly be correlated to a specific defect in protein kinase Cα in fibroblasts from Alzheimer patients.