Role of cholesterol metabolism in the pathogenesis of Alzheimer's disease.
OBJECTIVE
Cholesterol has been shown to stimulate the cleavage of amyloid precursor protein (APP) into amyloid peptides involved in Alzheimer's disease. However, high level of peripheral cholesterol as a risk factor for Alzheimer's disease is still debated. This current review provides an update of the recent literature on cholesterol and APP metabolisms in the brain.


RESULTS
First, a new relationship between neuronal APP and cholesterol has been shown in which this protein controls cholesterol turnover required for neuronal activity. Second, oxysterols are able to stimulate the synthesis of ATP-binding cassette transporters involved in the exchange of amyloid peptides between the blood and the brain. Third, changes in APP targeting to lipid rafts and/or their composition in cholesterol regulate amyloid peptide production.


CONCLUSIONS
These recent findings open new areas of investigations to control the neuronal activity and to decrease the amyloid peptide levels in brain, opening on new preventive and therapeutic strategies for Alzheimer's disease.
aINSERM UMR 894, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine bInstitut du Cerveau et de la Moelle, UPMC, INSERM UMR S 975, CNRS UMR 7225, Paris, France.
Bernadette
B
Allinquant
Christine
C
Clamagirand
Marie-Claude
MC
Potier
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D050356:Lipid Metabolism; D009474:Neurons / Q000378:metabolism; D012307:Risk Factors
D018528:ATP-Binding Cassette Transporters; D016564:Amyloid beta-Protein Precursor; D002784:Cholesterol