The p3 peptide, a naturally occurring fragment of the amyloid-β peptide (Aβ) found in Alzheimer's disease, has a greater aggregation propensity in vitro than full-length Aβ, but does not bind Cu2+

Cerebellar preamyloid from both Down's syndrome and Alzheimer's disease contains the p3 fragment (A beta 17-40/42) as a major amyloid-beta peptide (A beta) component. The p3 peptide was previously shown to form amyloid in vitro, but less readily than full-length A beta. Here we show that the p3 peptide has a greater beta-sheet-forming propensity than full-length A beta. Using circular dichroism spectroscopy we determined that in aqueous solutions the p3 peptide forms beta-sheet structure more readily than full-length A beta. The p3 peptide also has a lower alpha-helical propensity than full-length A beta in the structure-forming solvent trifluoroethanol. These results indicate that the lower amyloidogenicity of the p3 peptide is not related to an inability to form beta-sheet structure. In this study we also show that, unlike full-length A beta, the p3 peptide does not bind Cu2+ ions. This inability to bind copper ions may explain why the p3 peptide appears to play a lesser role in Down's syndrome and Alzheimer's disease related neurodegeneration than does full-length A beta.