Abstract: Described is a new class of small molecule inhibitors of amyloid &bgr; protein (A&bgr;) aggregation, based on apomorphine. These molecules target the nucleation phase of A&bgr; self-assembly and interfere effectively with aggregation of A&bgr; 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit A&bgr; amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active A&bgr; inhibitor.