A-BETA DEPOSITION INHIBITOR SCREEN USING SYNTHETIC AMYLOID

The formation, growth, and maturation of brain amyloid ''senile'' plaq ues are essential pathological processes in Alzheimer's disease (AD) a nd key targets for therapeutic intervention, The process of in vitro d eposition of A beta at physiological concentrations onto plaques in AD brain preparations has been well characterized, but is cumbersome for drug discovery. We describe here a high-throughput screen for inhibit ors of A beta deposition onto a synthetic template (synthaloid) of fib rillar A beta immobilized in a polymer matrix. Synthaloid is indisting uishable from plaques in AD brain (the natural template) in deposition kinetics, pH profile, and structure-activity relationships for both A beta analogs and inhibitors, Synthaloid, in contrast to current A bet a aggregation screens, accurately predicted inhibitor potency for A be ta deposition onto AD cortex preparations, validating its use in searc hing for agents that can slow the progression of AD and exposing a pre viously inaccessible target for drug discovery.