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

Soluble amyloid beta-protein (A beta) is normally present in the cerebrospi nal fluid (CSF) and plasma. However, it is fibrillized and deposited as pla ques in the brains of patients with Alzheimer's disease. Cerebrospinal flui d (CSF) contains several circulating proteins (apolipoprotein E, apolipopro tein J, and transthyretin) that bind to A beta. We report here that gelsoli n, a secretory protein, also binds to A beta in a concentration-dependent m anner. Under similar conditions, other proteins such as G-actin, protein ki nase 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 dissoc iation constants (K-d) of 1.38 and 2.55 mu M. A beta was found to co-immuno precipitate along with gelsolin from the plasma, suggesting that gelsolin-A beta complex exists under physiological conditions. The gelsolin-A beta co mplex was sodium dodecyl sulfate (SDS)stable in the absence of reducing age nt, but was dissociated when the SDS stop solution contained dithiothreitol (reducing agent). This study suggests that the function of secretory gelso lin in the CSF and plasma is to bind and sequester A beta. (C) 1999 Academi c Press.