Amyloid beta induces cellular relocalization and production of agrin and glypican-1
Timmer, Nienke M × van Horssen, Jack Otte-Holler, Irene Wilhelmus, Micha M. M David, Guido van Beers, Joyce de Waal, Rob M. W Verbeek, Marcel M #
Brain Research vol:1260 pages:38-46
The major component of senile plaques and vascular amyloid in Alzheimer's disease (AD) brains is the amyloid beta protein (A beta). Besides A beta, 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 A beta may influence production and expression of two major A beta-associated HSPG species, agrin and glypican-1. When human brain pericytes (HBP) were cultured in the presence of A beta, protein and mRNA expression of both agrin and glypican-1 were increased and more radioactive sulfate was incorporated in the glycosaminoglycan fraction of A beta-treated HBP. Furthermore, after A beta 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 A beta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these HSPG in AD lesions. (C) 2008 Published by Elsevier B.V.