Responsibility of lipid compositions for the amyloid ß assembly induced by ganglioside nanoclusters in mouse synaptosomal membranes

Teruhiko Matsubara, Takahiro Kojima, Ryoto Fukuda, Kazutoshi Iijma, Miwa Hirai, Naoki Yamamoto, Katsuhiko Yanagisawa, Toshinori Sato

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Abstract

The assembly of amyloid ß protein (Aß) on ganglioside-enriched microdomains in presynaptic neuronal membranes is involved in the onset of Alzheimer’s disease. We previously found that a highly enriched ganglioside domain generated in a reconstituted lipid bilayer composed of synaptosomal lipids functioned as an Aß-sensitive ganglioside nanocluster (ASIGN) that may induce a spherical Aß assembly. In the present study, the major lipid components of a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from an aged mouse brain were identified, and we demonstrate that the proportion of Aß-insensitive gangliosides such as GM3 directly affects the Aß assembly in synaptosomal membranes. Liquid chromatography coupled to mass spectrometry analyses indicated that ganglio a-series gangliosides (GM1, GM2, GM3, and GD1a) were abundant in DRM fractions. In addition, the GM3/GM1 ratio and the cholesterol content in the synaptosomal fraction differed from those in the non-synaptosomal fraction, in which GM1 and GM3 are sensitive and insensitive gangliosides, respectively. The highly enriched ganglioside nanocluster was identified by the surface topography of ternary mixed lipid bilayers composed of gangliosides, sphingomyelin, and cholesterol. Our results indicate that the composition of gangliosides is responsible for the characteristics of the nanocluster generated in the presynaptic neuronal membranes.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalPolymer Journal
DOIs
Publication statusAccepted/In press - 2018 Mar 22

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Gangliosides
Nanoclusters
Amyloid
Lipids
Membranes
Chemical analysis
Lipid bilayers
Cholesterol
Detergents
Liquid chromatography
Surface topography
Mass spectrometry
Brain
G(M1) Ganglioside
Serum Amyloid A Protein
Sphingomyelins

ASJC Scopus subject areas

  • Polymers and Plastics
  • Materials Chemistry

Cite this

Responsibility of lipid compositions for the amyloid ß assembly induced by ganglioside nanoclusters in mouse synaptosomal membranes. / Matsubara, Teruhiko; Kojima, Takahiro; Fukuda, Ryoto; Iijma, Kazutoshi; Hirai, Miwa; Yamamoto, Naoki; Yanagisawa, Katsuhiko; Sato, Toshinori.

In: Polymer Journal, 22.03.2018, p. 1-8.

Research output: Contribution to journalArticle

Matsubara, Teruhiko ; Kojima, Takahiro ; Fukuda, Ryoto ; Iijma, Kazutoshi ; Hirai, Miwa ; Yamamoto, Naoki ; Yanagisawa, Katsuhiko ; Sato, Toshinori. / Responsibility of lipid compositions for the amyloid ß assembly induced by ganglioside nanoclusters in mouse synaptosomal membranes. In: Polymer Journal. 2018 ; pp. 1-8.
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