beta-Amyloid (A beta) is the primary protein component of senile plaques in Alzheimer's disease (AD) and has been implicated in neurotoxicity associated with the disease. A beta aggregates readily in vitro and in vivo, and its toxicity has been linked to its aggregation state. Prevention of A beta aggregation has been investigated as a means to prevent A beta toxicity associated with AD. Recently we found that Hsp20 from Babesia bovis prevented both A beta aggregation and toxicity [S. Lee, K. Carson, A. Rice-Ficht, T. Good, Hsp20, a novel alpha-crystallin, prevents Abeta fibril formation and toxicity, Protein Sci. 14 (2005) 593-601.]. In this work, we examined the mechanism of Hsp20 interaction with A beta 1-40 and compared its activity to that of other small heat shock proteins, carrot Hsp17.7 and human Hsp27. While all three small heat shock proteins were able to prevent A beta aggregation, only Hsp20 was able to attenuate A beta toxicity in cultured SH-SY5Y cells. Understanding the mechanism of the Hsp20-A beta interaction may provide insights into the design of the next generation of A beta aggregation and toxicity inhibitors. (c) 2006 Elsevier Inc. All rights reserved.