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

PloS One
Naoto OikawaK Yanagisawa

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 ß-protein (Aß) into fibrils in the regions. On the basis of our previous findings that gangliosides facilitate the initiation of Aß 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 Aß 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 Aß 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 Aß assembly in the precuneus. Our results suggest that the local glycolipid environment play a critical ro...Continue Reading

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Citations

Jan 9, 2016·Molecular Neurobiology·Xi-Chen ZhuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Apr 24, 2015·Glycoconjugate Journal·Katsuhiko Yanagisawa
Jul 19, 2018·The Journal of Biological Chemistry·Teruhiko MatsubaraToshinori Sato
May 31, 2018·Scientific Reports·Yasutoyo YamasakiKatsuhiko Yanagisawa
Mar 10, 2021·Analytical and Bioanalytical Chemistry·Zhucui Li, Qibin Zhang
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Nov 18, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Teruhiko MatsubaraToshinori Sato
Feb 1, 2018·Analytical Chemistry·Rodell C Barrientos, Qibin Zhang

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Methods Mentioned

BETA
transgenic
AFM
transmission electron microscopy

Software Mentioned

ImageJ
GNU Image Manipulation Program ( GIMP

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