EVIDENCE FOR PRESENILIN-1 INVOLVEMENT IN AMYLOID ANGIOPATHY IN THE ALZHEIMERS-DISEASE-AFFECTED BRAIN

Citation
Y. Hayashi et al., EVIDENCE FOR PRESENILIN-1 INVOLVEMENT IN AMYLOID ANGIOPATHY IN THE ALZHEIMERS-DISEASE-AFFECTED BRAIN, Brain research, 789(2), 1998, pp. 307-314
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
Volume
789
Issue
2
Year of publication
1998
Pages
307 - 314
Database
ISI
SICI code
Abstract
Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). The role PS-1 plays in the pathogenesis of Alzheimer's disease (AD) remains unclear. Using a set of antibodies raised against PS-1 synthetic peptides, polyclonal antibody to amyloid beta protein (A beta) and end-specific antibodies against A beta 40 and A beta 42, immunohistochemical studies were performed on brain sections obtained from AD cases and controls. The PS-1 antibodies clearly stained amyloi d angiopathies in AD-affected brains, but no recognizable immunoreacti ons were observed in any other vessels free from amyloid involvement i n either AD-affected brains or controls. A beta antibodies and the end -specific antibody against A beta 40 also decorated amyloid angiopathi es, showing localization similar to that of PS-1. Western blot analyse s predominantly detected protein band polypeptide species of a 50 kDa band, presumably full-length PS-1 protein with N-terminus antisera, si nce these antibodies turned out to recognize a 50 kDa full-length band in cell lysate of transfected HeLa cell overexpressing PS-I. In addit ion, we recognized 30, 27, and 25 kDa proteins in both AD and control brain homogenate with these antibodies. In microvessel fractions extra cted from brain homogenates, the 50 and 27 kDa fragments were observed in AD-affected brains but not in those of controls. C-terminus rabbit antisera reacted strongly with the 33 and 27 kDa bands, and additiona lly detected a small amount of full-length PS-1 protein in extracts fr om AD and control brains. Our present data indicate that PS-1 might be involved in the pathogenesis of amyloid angiopathy in the AD brain. ( C) 1998 Elsevier Science B.V.