Cross‐seeding of wild‐type and hereditary variant‐type amyloid β‐proteins in the presence of gangliosides

• Published in: Journal of Neurochemistry
• Main Authors: Yamamoto, Naoki, Matsuzaki, Katsumi, Yanagisawa, Katsuhiko
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2005
• Subjects: Arctic
• Online Access: http://dx.doi.org/10.1111/j.1471-4159.2005.03444.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1471-4159.2005.03444.x; https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2005.03444.x

Abstract We investigated the molecular mechanism underlying the ganglioside‐induced initiation of the assembly of wild and hereditary variant‐type amyloid β‐proteins, including Arctic‐, Dutch‐, and Flemish‐type amyloid β‐proteins. We monitored the assembly of amyloid β‐protein by thioflavin‐T assay, western blotting and electron microscopy. We also examined how externally added amyloid β‐protein assembles in a cell culture. The assembly of wild‐, Arctic‐, Dutch‐, and Flemish‐type amyloid β‐proteins were accelerated in the presence of GM1, GM1, GM3 and GD3 gangliosides. Notably, all of these amyloid β‐proteins accelerated the assembly of different type of amyloid β‐protein, following prior binding to a specific ganglioside. A specific‐ganglioside‐bound form of variant‐type amyloid β‐protein was recognized by the antibody (4396C) specific to the GM1‐ganglioside‐induced altered conformation of wild‐type amyloid β‐protein. Moreover, the assembly of these amyloid β‐proteins in the presence of a specific ganglioside was markedly suppressed by coincubation with 4396C. This study suggests that cross‐seeding can occur between wild and hereditary variant‐type amyloid β‐proteins despite differences in their amino acid sequences.