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

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 chole...

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Bibliographic Details
Published in:Molecular neurodegeneration 2014-12, Vol.9 (1), p.60-60, Article 60
Main Authors: Marquer, Catherine, Laine, Jeanne, Dauphinot, Luce, Hanbouch, Linda, Lemercier-Neuillet, Camille, Pierrot, Nathalie, Bossers, Koen, Le, Mickael, Corlier, Fabian, Benstaali, Caroline, Saudou, Frédéric, Thinakaran, Gopal, Cartier, Nathalie, Octave, Jean-Noël, Duyckaerts, Charles, Potier, Marie-Claude
Format: Article
Language:English
Subjects:
Advertising executives
Alzheimer Disease - metabolism
Alzheimer's disease
Amyloid beta-Protein Precursor - metabolism
Animals
Apolipoproteins
Binding sites
Brain
Cell Membrane - metabolism
Cholesterol
Cholesterol - metabolism
Disease Models, Animal
Gene expression
Genes
Genetic aspects
Health aspects
Lipids
Memory - physiology
Metabolism
Microscopy
Neurons
Neurons - metabolism
Neurosciences
Ontology
Pathology
Phenotype
Physiological aspects
Proteins
Rats, Sprague-Dawley
Software
Statistical analysis
Target marketing
Transcriptome
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Summary: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. 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. 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.
ISSN:1750-1326
1750-1326
DOI:10.1186/1750-1326-9-60