Physical, morphological and functional differences between ph 5.8 and 7.4 aggregates of the Alzheimer's amyloid peptide Abeta.

Published

Journal Article

The Alzheimer's amyloid peptide Abeta(1-40) generates a turbid, Congo re-binding aggregation reaction product within minutes when incubated in the pH range 5 to 6. At pH 7.4, Abeta forms little or no aggregate in this time frame, requiring hours or days, rather than minutes, to complete fibril formation. The pH 5.8 aggregates are not amyloid fibrils, but rather appear in electron micrographs as a mixture of larger particles of different morphologies. These aggregates differ from classical fibrils by a number of other measures. Per mass of peptide aggregated, the pH 5.8 product binds less Congo red and thioflavin T than does aggregate grow in unstirred reactions at pH 7.4. Both the pH 5.8 and 7.4 aggregates exhibit light scattering at 90 degrees. However, while the pH 5.8 aggregate is visible in suspension by the light microscopy, and exhibits turbidity at 405 nm, the fibrils grown at pH 7.4 in an unstirred reaction are transparent. The two aggregate types do not interconvert in pH shift experiments. Most dramatically, and in contrast to fibrils grown at pH 7.4, the turbid aggregate generated at pH 5.8 is incapable of seeding fibril growth at pH 7.4. Although proteolytic processing of betaAPP to generate Abeta probably takes place in a low pH compartment of the cell, our results suggest that fibril formation is not likely to be initiated in such an environment.

Full Text

Cited Authors

  • Wood, SJ; Maleeff, B; Hart, T; Wetzel, R

Published Date

  • March 1996

Published In

Volume / Issue

  • 256 / 5

Start / End Page

  • 870 - 877

PubMed ID

  • 8601838

Pubmed Central ID

  • 8601838

Electronic International Standard Serial Number (EISSN)

  • 1089-8638

International Standard Serial Number (ISSN)

  • 0022-2836

Digital Object Identifier (DOI)

  • 10.1006/jmbi.1996.0133

Language

  • eng