Gelsolin inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils

Amyloid beta-protein (A beta) is present in soluble form in the plasma and cerebrospinal fluid (CSF) of normal people and patients with Alzheimer's di sease (AD). However, in AD patients, A beta gets fibrillized as the main co nstituent of amyloid plaques in the brain. Soluble synthetic A beta also fo rms amyloid-like fibrils when it is allowed to age. The mechanism that prev ents soluble A beta from fibrillization in biological fluids is not clear. We recently reported that gelsolin, a secretory protein, binds to A beta, a nd that gelsolin/A beta complex is present in the plasma [V.P.S. Chauhan, I . Ray, A. Chauhan, H.M. Wisniewski, Biochem. Biophys. Res. Commun. 258 (199 9) 241-246.]. We now studied the effect of gelsolin on A beta fibrillizatio n. Congo red staining and electron microscopic examination in negative stai ning of aged samples of A beta alone and A beta incubated with gelsolin sho wed that gelsolin inhibits the fibrillization of synthetic A beta 1-40 and A beta 1-42 at gelsolin to A beta molar ratio of 1:40. In addition, gelsoli n also defibrillized the preformed fibrils of A beta 1-40 and A beta 1-42 i n a time-dependent manner. These results suggest that gelsolin functions as an anti-amyloidogenic protein in the plasma and CSF, where it prevents A b eta from fibrillization, and helps to maintain it in the soluble form. (C) 2000 Published by Elsevier Science B.V. All rights reserved.