Amyloid beta induces cellular relocalization and production of agrin and glypican-1.
The major component of senile plaques and vascular amyloid in Alzheimer's disease (AD) brains is the amyloid beta protein (Abeta). Besides Abeta, several other proteins have been identified in these lesions, in particular heparan sulfate proteoglycans (HSPG). However, it is still unclear, what causes the excessive accumulation of HSPG in AD brains. Therefore, we investigated if Abeta may influence production and expression of two major Abeta-associated HSPG species, agrin and glypican-1. When human brain pericytes (HBP) were cultured in the presence of Abeta, protein and mRNA expression of both agrin and glypican-1 were increased and more radioactive sulfate was incorporated in the glycosaminoglycan fraction of Abeta-treated HBP. Furthermore, after Abeta treatment, these HSPG were found in association with the amyloid fibrils attached to the cell membrane, in contrast to the intracellular agrin and glypican-1 staining observed in untreated cells. We conclude that Abeta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these HSPG in AD lesions.
Timmer
Nienke M
NM
Department of Neurology, Laboratory of Pediatrics and Neurology, Donders Centre for Brain, Cognition and Behaviour, Alzheimer Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. n.timmer@cukz.umcn.nl
van Horssen
Jack
J
Otte-Holler
Irene
I
Wilhelmus
Micha M M
MM
David
Guido
G
van Beers
Joyce
J
de Waal
Rob M W
RM
Verbeek
Marcel M
MM
D018171:Agrin / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D053673:Glypicans / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D020286:Pericytes / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D013462:Sulfur Radioisotopes
D018171:Agrin; D016229:Amyloid beta-Peptides; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes