Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid β-protein fibrillogenesis

Naoki Yamamoto, Teruhiko Matsubara, Toshinori Sato, Katsuhiko Yanagisawa

研究成果: Article査読

95 被引用数 (Scopus)

抄録

The deposition of amyloid β-protein (Aβ) is an invariable feature of Alzheimer's disease (AD); however, the biological mechanism underlying Aβ assembly into fibrils in the brain remains unclear. Here, we show that a high-density cluster of GM1 ganglioside (GM1), which was detected by the specific binding of a novel peptide (p3), appeared selectively on synaptosomes prepared from aged mouse brains. Notably, the synaptosomes bearing the high-density GM1 cluster showed extraordinary potency to induce Aβ assembly, which was suppressed by an antibody specific to GM1-bound Aβ, an endogenous seed for AD amyloid. Together with evidence that Aβ deposition starts at presynaptic terminals in the AD brain and that GM1 levels significantly increase in amyloid-positive synaptosomes prepared from the AD brain, our results suggest that the age-dependent high-density GM1 clustering at presynaptic neuritic terminals is a critical step for Aβ deposition in AD.

本文言語English
ページ(範囲)2717-2726
ページ数10
ジャーナルBiochimica et Biophysica Acta - Biomembranes
1778
12
DOI
出版ステータスPublished - 2008 12

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 細胞生物学

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