Small heat shock protein (sHsp) is a molecular chaperone with a conserved alpha-crystallin domain that can prevent protein aggregation. It has been shown that sHsps exist as oligomers (12-40 mer) and their dissociation into small dimers or oligomers is functionally important. Since several sHsps are upregulated and co-localized with amyloid-beta (A beta) in senile plaques of patients with Alzheimer's disease (AD), sHsps are thought to be involved in AD. Previous studies have also shown that sHsp can prevent A beta aggregation in vitro. However, it remains unclear how the quaternary structure of sHsp influences A beta aggregation. In this study, we report for the first time the effect of the quaternary structure of sHsp on A beta aggregation using sHsp from the fission yeast Schizosaccharomyces pombe (SpHsp16.0) showing a clear temperature-dependent structural transition between an oligomer (30 degrees C) and dimer (50 degrees C) state. A beta aggregation was inhibited by the oligomeric form of SpHsp16.0. In contrast, amyloid fibrils were formed in the presence of dimeric SpHsp16.0. Interestingly, these amyloid fibrils consisted of both A beta and SpHsp16.0 and showed a low ThT intensity and low cytotoxicity due to their low binding affinity to the cell surface. These results suggest the formation of novel fibrillar A beta amyloid with different characteristics from that of the authentic A beta amyloid fibrils formed in the absence of sHsp. Our results also suggest the potential protective role of sHsp in AD under stress conditions. (C) 2012 Elsevier Inc. All rights reserved.