DEFECTIVE PHORBOL ESTER-STIMULATED SECRETION OF BETA-AMYLOID PRECURSOR PROTEIN FROM ALZHEIMERS-DISEASE FIBROBLASTS

The present study shows that cultured fibroblasts from sporadic Alzhei mer's disease patients are deficient in protein kinase C-regulated sec retion of amyloid precursor protein. In particular, Alzheimer fibrobla sts show a reduced basal secretion and a reduced response at low conce ntrations of phorbol-12,13-dibutyrate, with an EC(50) twofold higher t han control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly bi: correla ted to a specific defect in protein kinase C alpha in fibroblasts from Alzheimer patients.