Small heat shock proteins inhibit in vitro A beta(1-42) amyloidogenesis.

We demonstrate that small heat shock proteins (sHsp) inhibit in vitro amyloid formation by the Alzheimer's A beta(1-42) polypeptide as detected by a thioflavine T fluorescence assay and electron microscopy. Human sHsp27 (0.50-3.0 microM) inhibited amyloid formation from 20 microM A beta(1-42) by 23-75%, in 24 h. In contrast, treatment of pre-formed amyloid with 0.5-3.0 microM sHsp27 only reduced the fluorescence signal by 6-36%. The data suggest that ordered fibril formation may represent a form of off-pathway aggregation that can be prevented by chaperone action. The data raise the possibility that age-related changes in chaperone function could contribute toward the pathogenesis of Alzheimer's and other amyloid-associated diseases.