Purpose of review 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.
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.
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.