Cholesterol in Alzheimer's disease and other amyloidogenic disorders

• Published in: Sub-cellular biochemistry Vol. 51; p. 47
• Main Authors: Harris, J Robin, Milton, Nathaniel G N
• Format: Journal Article
• Language: English
• Published: United States 01.01.2010
• Subjects: Alzheimer Disease - complications; Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Amyloid - biosynthesis; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases - metabolism; Apolipoproteins E - metabolism; Atherosclerosis; Brain - metabolism; Cholesterol - metabolism; G(M1) Ganglioside - physiology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Neurons - metabolism; Oxidative Stress - physiology; tau Proteins - metabolism; Tauopathies - physiopathology
• ISSN: 0306-0225
• DOI: 10.1007/978-90-481-8622-8_2

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.