title: Increasing membrane cholesterol of neurons in culture recapitulates Alzheimer's disease early phenotypes.
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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Marquer
authors.forename: Jeanne
authors.initials: J
authors.lastname: Laine
authors.forename: Luce
authors.initials: L
authors.lastname: Dauphinot
authors.forename: Linda
authors.initials: L
authors.lastname: Hanbouch
authors.forename: Camille
authors.initials: C
authors.lastname: Lemercier-Neuillet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pierrot
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
authors.forename: Mickael
authors.initials: M
authors.lastname: Le
authors.forename: Fabian
authors.initials: F
authors.lastname: Corlier
authors.forename: Caroline
authors.initials: C
authors.lastname: Benstaali
authors.forename: Frédéric
authors.initials: F
authors.lastname: Saudou
authors.forename: Gopal
authors.initials: G
authors.lastname: Thinakaran
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cartier
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Octave
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France. marie-claude.potier@upmc.fr.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Potier
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D008568:Memory / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D059467:Transcriptome
chemical_list: D016564:Amyloid beta-Protein Precursor; D002784:Cholesterol