Search

We demonstrate that small heat shock proteins (sHsp) inhibit in vitro amyloid formation by the Alzheimer's Aβ 1–42polypeptide as detected by a thioflavine T fluorescence assay and electron microscopy. Human sHsp27 (0.50–3.0 μM) inhibited amyloid formation from 20 μM Aβ 1–42by 23–75% in 24 h. In contrast, treatment of pre-formed amyloid with 0.5–3.0 μM 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.