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.
Curr Opin Clin Nutr Metab Care. 2014 Jul;17(4):319-23. doi: 10.1097/MCO.0000000000000069.
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.
胆固醇已被证明能刺激淀粉样前体蛋白（APP）裂解成阿尔茨海默病相关的淀粉样肽。然而，外周胆固醇水平高作为阿尔茨海默病的一个风险因素仍存在争议。本综述提供了关于胆固醇和 APP 代谢物在大脑中的最新文献的更新。
首先，在神经元 APP 和胆固醇之间显示出一种新的关系，其中该蛋白控制神经元活动所需的胆固醇周转。其次，氧化固醇能够刺激参与血液和大脑之间淀粉样肽交换的 ABC 转运蛋白的合成。第三，APP 向脂筏的靶向变化和/或胆固醇中其组成调节淀粉样肽的产生。
这些新的发现为控制神经元活性和降低大脑中的淀粉样肽水平开辟了新的研究领域，为阿尔茨海默病的预防和治疗策略开辟了新的途径。
