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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2014

Open Access 01-12-2014 | Research article

Increasing membrane cholesterol of neurons in culture recapitulates Alzheimer’s disease early phenotypes

Authors: Catherine Marquer, Jeanne Laine, Luce Dauphinot, Linda Hanbouch, Camille Lemercier-Neuillet, Nathalie Pierrot, Koen Bossers, Mickael Le, Fabian Corlier, Caroline Benstaali, Frédéric Saudou, Gopal Thinakaran, Nathalie Cartier, Jean-Noël Octave, Charles Duyckaerts, Marie-Claude Potier

Published in: Molecular Neurodegeneration | Issue 1/2014

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Abstract

Background

It is suspected that excess of brain cholesterol plays a role in Alzheimer’s disease (AD). Membrane-associated cholesterol was shown to be increased in the brain of individuals with sporadic AD and to correlate with the severity of the disease. We hypothesized that an increase of membrane cholesterol could trigger sporadic AD early phenotypes.

Results

We thus acutely loaded the plasma membrane of cultured neurons with cholesterol to reach the 30% increase observed in AD brains. We found changes in gene expression profiles that are reminiscent of early AD stages. We also observed early AD cellular phenotypes. Indeed we found enlarged and aggregated early endosomes using confocal and electron microscopy after immunocytochemistry. In addition amyloid precursor protein vesicular transport was inhibited in neuronal processes, as seen by live-imaging. Finally transient membrane cholesterol loading lead to significantly increased amyloid-β42 secretion.

Conclusions

Membrane cholesterol increase in cultured neurons reproduces most early AD changes and could thus be a relevant model for deciphering AD mechanisms and identifying new therapeutic targets.
Appendix
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Metadata
Title
Increasing membrane cholesterol of neurons in culture recapitulates Alzheimer’s disease early phenotypes
Authors
Catherine Marquer
Jeanne Laine
Luce Dauphinot
Linda Hanbouch
Camille Lemercier-Neuillet
Nathalie Pierrot
Koen Bossers
Mickael Le
Fabian Corlier
Caroline Benstaali
Frédéric Saudou
Gopal Thinakaran
Nathalie Cartier
Jean-Noël Octave
Charles Duyckaerts
Marie-Claude Potier
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2014
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-9-60

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