EVIDENCE THAT GLYPICAN IS A RECEPTOR MEDIATING BETA-AMYLOID NEUROTOXICITY IN PC12 CELLS

Docking of beta-amyloid fibrils to neuronal or glial cell membranes ma y be an early, necessary and intervenable step during the progression of Alzheimer's disease. Formation of neurofibrillary tangles and amylo id plaques as well as neurotoxicity and inflammation may be direct or indirect consequences. In an attempt to find a receptor that mediates those effects, we assessed rat pheochromocytoma PC12 cell 3-[4,5-dimet hylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction afte r addition of P-amyloid to the culture medium. Presence of competitive substances in the medium, cell-surface treatment and specific block o f cellular synthesis pathways helped to identify the heparan sulphate moiety of a glycosylphosphatidylinositol-anchored protein likely to re present glypican as a possible receptor mediating beta-amyloid neuroto xicity.