Alzheimer's disease and cholesterol: the fat connection.
Since the discovery of the significance of the cholesterol-carrying apolipoprotein E and cholesterolaemia as major risk factors for Alzheimer's Disease (AD) there has been a mounting interest in the role of this lipid as a possible pathogenic agent. In this review we analyse the current evidence linking cholesterol metabolism and regulation in the CNS with the known mechanisms underlying the development of Alzheimer's Disease. Cholesterol is known to affect amyloid-beta generation and toxicity, although it must be considered that the results studies using the statin class of drugs to lower plasma cholesterol may be affected by other effects associated with these drugs. Finally, we report some of our results pointing at the interplay between neurons and astrocytes and NADPH oxidase activation as a new candidate mechanism linking cholesterol and AD pathology.
Canevari
Laura
L
Miriam Marks Division of Neurochemistry, Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK. l.canevari@imperial.ac.uk
Clark
John B
JB
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000633:toxicity; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019255:NADPH Oxidases