Density of GM1 in nanoclusters is a critical factor in the formation of a spherical assembly of amyloid β-protein on synaptic plasma membranes.

Abstract

The deposition of amyloid β-protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD). We previously found that the ganglioside-enriched microdomains (ganglioside clusters) in presynaptic neuronal membranes play a key role in the initiation of the Aβ assembly process. However, not all ganglioside clusters accelerate Aβ assembly. In the present study, we directly observed a spherical Aβ in an atomic force microscopic study on the morphology of a reconstituted lipid bilayer composed of lipids that were extracted from a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from aged mouse brain. The Aβ assembly was generated on a distinctive GM1 domain, which was characterized as the Aβ-sensitive ganglioside nanocluster (ASIGN). By using an artificial GM1 cluster-binding peptide, ASIGN was found to have a high density of GM1; therefore, there would be a critical density of GM1 in nanoclusters to induce Aβ binding and assembly. These results suggest that ganglioside-bound Aβ (GAβ), which acts as an endogenous seed for Aβ fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes.

• Authors: Teruhiko Matsubara, Kazutoshi Iijima, Naoki Yamamoto, Katsuhiko Yanagisawa, Toshinori Sato
• Journal: Langmuir : the ACS journal of surfaces and colloids (Langmuir) Vol. 29 Issue 7 Pg. 2258-64 (Feb 19 2013) ISSN: 1520-5827 [Electronic] United States
• PMID: 23294326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Lipid Bilayers
• G(M1) Ganglioside

Topics

• Amyloid beta-Peptides (chemistry)
• Animals
• Cell Membrane (chemistry)
• G(M1) Ganglioside (chemistry)
• Lipid Bilayers (chemistry)
• Mice
• Microscopy, Atomic Force (methods)
• Synaptic Membranes (chemistry)
• Synaptosomes (chemistry)