Abstract: Described is a new class of small molecule inhibitors of amyloid ? protein (A?) aggregation, based on apomorphine. These molecules target the nucleation phase of A? self-assembly and interfere effectively with aggregation of A? 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? 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? inhibitor.