Imbalance in fatty-acid-chain length of gangliosides triggers Alzheimer amyloid deposition in the precuneus

Naoto Oikawa, Teruhiko Matsubara, Ryoto Fukuda, Hanaki Yasumori, Hiroyuki Hatsuta, Shigeo Murayama, Toshinori Sato, Akemi Suzuki, Katsuhiko Yanagisawa

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Abstract

Amyloid deposition, a crucial event of Alzheimer's disease (AD), emerges in distinct brain regions. A key question is what triggers the assembly of the monomeric amyloid β-protein (Aβ) into fibrils in the regions. On the basis of our previous findings that gangliosides facilitate the initiation of Aβ assembly at presynaptic neuritic terminals, we investigated how lipids, including gangliosides, cholesterol and sphingomyelin, extracted from synaptic plasma membranes (SPMs) isolated from autopsy brains were involved in the Aβ assembly. We focused on two regions of the cerebral cortex; precuneus and calcarine cortex, one of the most vulnerable and one of the most resistant regions to amyloid deposition, respectively. Here, we show that lipids extracted from SPMs isolated from the amyloid-bearing precuneus, but neither the amyloid-free precuneus nor the calcarine cortex, markedly accelerate the Aβ assembly in vitro. Through liquid chromatography-mass spectrometry of the lipids, we identified an increase in the ratio of the level of GD1b-ganglioside containing C20:0 fatty acid to that containing C18:0 as a cause of the enhanced Aβ assembly in the precuneus. Our results suggest that the local glycolipid environment play a critical role in the initiation of Alzheimer amyloid deposition.

Original languageEnglish
Article numbere0121356
JournalPloS one
Volume10
Issue number3
DOIs
Publication statusPublished - 2015 Mar 23

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Oikawa, N., Matsubara, T., Fukuda, R., Yasumori, H., Hatsuta, H., Murayama, S., Sato, T., Suzuki, A., & Yanagisawa, K. (2015). Imbalance in fatty-acid-chain length of gangliosides triggers Alzheimer amyloid deposition in the precuneus. PloS one, 10(3), [e0121356]. https://doi.org/10.1371/journal.pone.0121356