Cholesterol in Alzheimer's disease and other amyloidogenic disorders.
The complex association of cholesterol metabolism and Alzheimer's disease is presented in depth, including the possible benefits to be gained from cholesterol-lowering statin therapy. Then follows a survey of the role of neuronal membrane cholesterol in Abeta pore formation and Abeta fibrillogenesis, together with the link with membrane raft domains and gangliosides. The contribution of structural studies to Abeta fibrillogenesis, using TEM and AFM, is given some emphasis. The role of apolipoprotein E and its isoforms, in particular ApoE4, in cholesterol and Abeta binding is presented, in relation to genetic risk factors for Alzheimer's disease. Increasing evidence suggests that cholesterol oxidation products are of importance in generation of Alzheimer's disease, possibly induced by Abeta-produced hydrogen peroxide. The body of evidence for a link between cholesterol in atherosclerosis and Alzheimer's disease is increasing, along with an associated inflammatory response. The possible role of cholesterol in tau fibrillization, tauopathies and in some other non-Abeta amyloidogenic disorders is surveyed.
Harris
J Robin
JR
Institute of Zoology, University of Mainz, D-55099, Mainz, Germany. rharris@uni-mainz.de
Milton
Nathaniel G N
NG
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D000682:Amyloid / Q000096:biosynthesis; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D024801:Tauopathies / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016875:tau Proteins; D005677:G(M1) Ganglioside; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases