Cholesterol in neurologic disorders of the elderly: stroke and Alzheimer's disease.
Mechanisms for the regulation of intracellular cholesterol levels in various types of brain and vascular cells are of considerable importance in our understanding of the pathogenesis of a variety of diseases, particularly atherosclerosis and Alzheimer's disease (AD). It is increasingly clear that conversion of brain cholesterol into 24-hydroxycholesterol and its subsequent release into the periphery is important for the maintenance of brain cholesterol homeostasis. Recent studies have shown elevated plasma concentrations of 24-hydroxycholesterol in patients with AD and vascular dementia, suggesting increased brain cholesterol turnover during neurodegeneration. The oxygenases involved in the degradation and excretion of cholesterol, including the cholesterol 24-hydroxylase and the 27-hydroxylase, are enzymes of the cytochrome P-450 family. This review focuses on the newly recognized importance of cholesterol and its oxygenated metabolites in the pathogenesis of ischemic stroke and AD. The reduction in stroke and AD risk in patients treated with cholesterol-lowering statins is also discussed.
Reiss
Allison B
AB
Department of Medicine, New York University School of Medicine, New Bellevue 16N1, 550 First Avenue, New York, NY 10016, USA. reissa01@popmail.med.nyu.edu
Siller
Keith A
KA
Rahman
Mohammad M
MM
Chan
Edwin S L
ES
Ghiso
Jorge
J
de Leon
Mony J
MJ
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D002537:Intracranial Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013250:Steroid Hydroxylases / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C044563:24-hydroxycholesterol; D002784:Cholesterol; D013250:Steroid Hydroxylases