Autoantibodies to redox-modified oligomeric aβ are attenuated in the plasma of Alzheimer's disease patients

Abstract

Accumulation of Aβ protein in β-amyloid deposits is a hallmark event in Alzheimer's disease (AD). Recent findings suggest anti-Aβ autoantibodies may have a role in AD pathology. However, a consensus has yet to emerge as to whether endogenous anti-Aβ autoantibodies are elevated, depressed, or unchanged in AD patients. Whereas experiments to date have used synthetic un-modified, monomeric Aβ (Aβmon) to test autoimmunity, up to 40% of the Aβ pool in AD brain consists of low molecular weight oligomeric cross-linked β-amyloid protein species (CAPS). Recent studies also suggest that CAPS may be the primary neurotosic agent in AD. In the present study, AD and nondemented control plasma were analyzed for immunoreactivity to CAPS and Aβmon. Plasma of both nondemented and AD patients were found to contain autoantibodies specific for soluble CAPS. Nondemented control and AD plasmas demonstrated similar immunoreactivity to Aβmon. In contrast, anti-CAPS antibodies in AD plasma were found to be significantly reduced compared with nondemented controls (p = 0.018). Furthermore, age at onset for AD correlated significantly (p = 0.041) with plasma immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are depleted in AD patients and raise the prospect that immunization with anti-CAPS antibodies might provide therapeutic benefit for AD. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.