Binding of gelsolin, a secretory protein, to amyloid β-protein

Soluble amyloid beta-protein (A beta) is normally present in the cerebrospinal fluid (CSF) and plasma. However, it is fibrillized and deposited as plaques in the brains of patients with Alzheimer's disease. Cerebrospinal fluid (CSF) contains several circulating proteins (apolipoprotein E, apolipoprotein J, and transthyretin) that bind to A beta. We report here that gelsolin, a secretory protein, also binds to A beta in a concentration-dependent manner. Under similar conditions, other proteins such as G-actin, protein kinase C, polyglutamic acid, and gelatin did not bind to A beta. Solid phase binding assays showed two A beta binding sites on gelsolin that have dissociation constants (K-d) of 1.38 and 2.55 mu M. A beta was found to co-immunoprecipitate along with gelsolin from the plasma, suggesting that gelsolin-A beta complex exists under physiological conditions. The gelsolin-A beta complex was sodium dodecyl sulfate (SDS)stable in the absence of reducing agent, but was dissociated when the SDS stop solution contained dithiothreitol (reducing agent). This study suggests that the function of secretory gelsolin in the CSF and plasma is to bind and sequester A beta. (C) 1999 Academic Press.