Unknown,Transcriptomics,Genomics,Proteomics

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Increase in membrane cholesterol of neurons in culture recapitulates AlzheimerM-bM-^@M-^Ys disease early phenotypes.


ABSTRACT: Levels of membrane-associated cholesterol were shown to be increased in the brain of individuals with sporadic AlzheimerM-bM-^@M-^Ys disease (AD) and correlated with the severity of the disease. We previously found that heavy membrane cholesterol burden promotes amyloid precursor protein (APP) endocytosis and processing, leading to increased amyloid-M-oM-^AM-"M-oM-^@M- M-oM-^@M-(AM-oM-^AM-") secretion. We hypothesized that such an increase of cholesterol could trigger sporadic AD. We thus acutely loaded the plasma membrane of neurons in culture with cholesterol to reach the 30 % increase observed in AD brains. We showed by multiplex electro-chemiluminescence immuno-assay that transient membrane cholesterol loading produced a significant increase of AM-oM-^AM-"42 secretion. We also found that early endosomes were enlarged and more prone to aggregation using confocal and electron microscopy and that APP vesicular transport in neuronal processes was slowed down using fluorescence live-imaging. In addition, treatment of neurons with cholesterol induced changes in gene expression profile that are reminiscent of early AD. This model of membrane cholesterol increase in cultured neurons reproduces most of early AD changes and could thus be relevant for deciphering early mechanisms and design new targets for sporadic AD. In this study, we loaded the plasma membrane of neurons with 30% more cholesterol and observed the effects on gene expression. We compared gene expression of primary hippocampal neurons treated or not with cholesterol using 4 independant replicates in each group.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Luce Dauphinot 

PROVIDER: E-GEOD-46221 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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<h4>Background</h4>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.<h4>Results</h4>We thus acutely loaded the plasma membrane of cultured neurons with cholesterol to reach the 30% increase observed in AD  ...[more]

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