Polymerization of the amyloid beta-peptide (A beta) has been identified as
a major feature of the pathogenesis of Alzheimer's disease (AD). Inhibition
of the formation of these toxic polymers of A beta has thus emerged as an
approach to developing therapeutics for AD. Techniques for studying A beta
polymerization include the use of fibril nucleation and extension assays in
a variety of formats. Detection of polymeric forms of A beta has been achi
eved using turbidity, dye binding, light scattering and toxicity among othe
r methods. Direct and indirect methods have been described for the measurem
ent of binding affinities for A beta fibrils. Imaging techniques include el
ectron microscopy, X-ray diffraction and atomic force microscopy. These tec
hniques have been used to characterize different classes of compounds that
inhibit the formation of A beta polymers. These compounds include dyes such
as Congo Red, the antibiotic rifampicin, the anthracycline 4'-iodo-4'-deox
ydoxorubicin, and a large variety of A beta-derived peptides and modified p
eptides, among other reported inhibitors. (C) 2000 Elsevier Science B.V. Al
l rights reserved.