Figure 1.

Assessment of prefibrillar selectivity in a focused indole collection. A) Schematic of the Aβ-aggregation pathway highlights some prefibril structures (e.g., monomers, dimers, trimers, tetramers, protofibrils, and globular oligomers) that are believed to eventually form fibrils. This schematic is not meant to imply any particular order to the aggregation event, only to show that multiple types of structures are observed and that these can be broadly classified as either prefibrillar or fibrillar. B) A library of 37 indole-containing compounds was screened for changes in fluorescence in the presence of either Aβ prefibrils or fibrils. Prefibrillar selectivity is defined as the ratio (prefibril/fibril) of the fluorescence change. The results from ten compounds (gray bars) that showed greater prefibrillar selectivity relative to the initial “hit” indole (6.3; dashed line), are highlighted. All compounds were tested in triplicate and the error bars represent the standard deviation.