pH-Dependent Aggregate Forms and Conformation of Alzheimer Amyloid -Peptide (12-24)

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Abstract
The conformational transition to a β-structure and the aggregation process of Alzheimer amyloid β-peptide (12–24) [abbreviated as Aβ12–24] were studied. The influence of sample dissolution methods for the aggregate structure was examined by electron microscopy (EM). The difference in the width of the aggregate of Aβ12–24 depended on the pH immediately after sample dissolution. Two types of sample dissolution methods, F and R, were employed. For dissolution method F, the peptide sample was immediately dissolved in water and then adjusted to pH 2.2 by adding buffer, while for dissolution method R, the peptide was directly dissolved in the buffer solution. In the latter case, the starting pH was 3.0. Slight fibrils (10–12 nm in diameter) were observed with method F, and wider ribbon-like aggregates (17–20 nm in diameter) with method R, despite the same pH range. A difference between methods F and R was also detected in the CD spectra, especially at pHs near 5.0. The CD intensity of the 214 nm band with method R changed with pH, with the highest value at pH 3.7, whereas that with method F was unchanged at pHs below 5.0. The temperature-dependent CD results showed that a thermostable aggregate of Aβ12–24 occurs at higher pHs than 3.0. NMR analysis showed that deprotonation of the C-terminal carboxylate group in Aβ12–24 triggered the aggregate formation, and the transition from a random coil to a β-conformation in the C-terminal region of V18–V24 was detected on analysis of the 3JαN coupling constant in the pH range of 2.2 to 3.0.

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