Proteoglycans in the pathogenesis of Alzheimer's disease and other amyloidoses

Abstract

Proteoglycans and the amyloid P component are two constituents of amyloid that appear to be present regardless of the type of amyloid protein deposited, the extent of amyloid deposition and the tissue or organ involved. This article reviews the literature concerning proteoglycans and/or glycosaminoglycans in amyloidosis and describes recent studies which demonstrate their localization to the characteristic lesions of Alzheimer's disease and the amyloid plaques containing PrP protein in the prion diseases. Additionally, the possible interaction of proteoglycans with various amyloidogenic proteins, including the beta-amyloid protein in Alzheimer's disease is discussed. It is postulated that proteoglycans localized to a number of different amyloids play a common role in the pathogenesis of amyloidosis. Some of these hypothesized roles include 1) inducing amyloidogenic precursor proteins to form amyloid fibrils containing a predominant beta-pleated sheet structure, 2) influencing amyloid deposition to occur at specific anatomical sites within tissues and/or 3) aiding in prevention of amyloid degradation once amyloid has formed.