Brain Cholesterol, Statins and Alzheimer's Disease

Pharmacopsychiatry

Volumn 36, Issue SUPPL. 2, 2003, Pages

  Kirsch, C ^a   Eckert, G P ^a   Koudinov, A R ^b   Muller W E ^a  

^a GOETHE UNIVERSITY   (Germany)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Alzheimer's Disease; Brain; Cholesterol; Membrane; Statins

Indexed keywords

AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E; CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; NITRIC OXIDE; PRAVASTATIN; SIMVASTATIN;

ALZHEIMER DISEASE; BLOOD BRAIN BARRIER; BRAIN; BRAIN MEMBRANE; CENTRAL NERVOUS SYSTEM; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL DIET; CHOLESTEROL SYNTHESIS; CONFERENCE PAPER; DRUG EFFECT; DRUG MECHANISM; DRUG METABOLISM; EVIDENCE BASED MEDICINE; HOMEOSTASIS; HUMAN; IN VIVO STUDY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN MODIFICATION; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANALYSIS OF VARIANCE; ANIMALS; ANTICHOLESTEREMIC AGENTS; APOLIPOPROTEINS E; BRAIN; BRAIN CHEMISTRY; CELL LINE; CELL MEMBRANE; CHOLESTEROL; CHOLESTEROL, DIETARY; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FLUORESCENCE; HUMANS; LIVER; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEUROFIBRILLARY TANGLES; PRECIPITIN TESTS; RATS; RATS, WISTAR; TIME FACTORS; TRANSFECTION;

EID: 0242288696     PISSN: 01763679     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (71)

1. Auerbach BJ, Parks JS, Applebaum-Bowden D. A rapid and sensitive micro-assay for the enzymatic determination of plasma and lipoprotein cholesterol. J Lipid Res 1990; 31: 738-742
2. Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med 2000; 32: 164-176
3. Bjorkhem I, Lütjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 1998; 39: 1594-1600
4. Bodovitz S, Klein WL. Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein. J Biol Chem 1996; 271: 4436-4440
5. Botti RE, Triscari J, Pan HY, Zayat J. Concentrations of pravastatin and lovastatin in cerebrospinal fluid in healthy subjects. Clin Neuropharmacol 1991; 14: 256-261
6. Colton CA, Brown CM, Czapiga M, Vitek MP. Apolipoprotein-E allele-specific regulation of nitric oxide production. Ann N Y Acad Sci 2002; 962: 212-225
7. Corsini A, Bernini F, Quarato P, Donetti E, Bellosta S, Fumagalli R, Paoletti R, Soma VM. Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Cardiology 1996; 87: 458-468
8. Das UN. Essential fatty acids as possible mediators of the actions of statins. Prostaglandins Leukot Essent Fatty Acids 2001; 65: 37-40
9. Das UN. Nitric oxide as the mediator of the antiosteoporotic actions actions of estrogen, statins and essential fatty acids. Exp Biol Med 2002; 227: 88-93
10. Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol 2001; 12: 105-112
11. Eckert GP, Igbavboa U, Müller WE, Wood WG. Lipid rafts of purified mouse brain synaptosomes prepared with or without detergent reveal different lipid and protein domains. Brain Res 2003; 962: 144-150
12. Eckert GP, Kirsch C, Mueller WE. Differential effects of lovastatin treatment on brain cholesterol levels in normal and ApoE-deficient mice. Neuroreport 2001; 12: 883-887
13. Eckert GP, Wood WG, Muller WE. Effects of aging and beta-amyloid on the properties of brain synaptic and mitochondrial membranes. J Neural Transm 2001 ; 108: 1051-1064
14. Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 1998; 95: 8880-8885
15. Fassbender K, Simons M, Bergmann C, Stroick M, Lütjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci USA 2001; 98: 5856-5861
16. Fassbender K, Stroick M, Bertsch T, Ragoschke A, Kuehl S, Walter S, Walter J, Brechtel K, Muehlhauser F, von Bergmann K, Lütjohann D. Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 2002; 59: 1257-1258
17. Feron O, Dessy C, Desager JP, Balligand JL. Hydroxy-methylglutaryl- coenzyme A reductase inhibition promotes endothelial nitric oxide synthase activation through a decrease in caveolin abundance. Circulation 2001; 103: 113-118
18. Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM. The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 1999; 10: 1699-1705
19. Gimpl G, Burger K, Fahrenholz F. Cholesterol as modulator of receptor function. Biochemistry 1997; 36: 10 959-10 974
20. Glomset JA, Farnsworth CC. Role of protein modification reactions in programming interactions between ras-related GTPases and cell membranes. Annu Rev Cell Biol 1994; 10: 181-205
21. Golde TE, Eckman CB. Cholesterol modulation as an emerging strategy for the treatment of Alzheimer's disease. Drug Discov Today 2001; 6: 1049-1055
22. Gong JS, Sawamura N, Zou K, Sakai J, Yanagisawa K, Michikawa M. Amyloid β-protein affects cholesterol metabolism in cultured neurons: Implications for a pivotal role of cholesterol in the amyloid cascade. J Neurosci Res 2002; 70: 438-446
23. Hajjar I, Schumpert J, Hirth V, Wieland D, Eleazer GP. The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol: Medical Sciences 2002; 7: M414-418
24. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 1998; 19: 26-37
25. Hayashi H, Igbavboa U, Hamanaka H, Kobayashi M, Fujita SC, Wood WG, Yanagisawa K. Cholesterol is increased in the exofacial leaflet of synaptic plasma membranes of human apolipoprotein E4 knock-in mice. Neuroreport 2002; 13: 383-386
26. Igbavboa U, Avdulov NA, Chochina SV, Wood WG. Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins. J Neurochem 1997; 69: 1661-1667
27. Igbavboa U, Avdulov NA, Schroeder F, Wood WG. Increasing age alters transbilayer fluidity and cholesterol asymmetry in synaptic plasma membranes of mice. J Neurochem 1996; 66: 1717-1725
28. Igbavboa U, Hamilton J, Kim HY, Sun GY, Wood WG. A new role for apolipoprotein E: modulating transport of polyunsaturated phospholipid molecular species in synaptic plasma membranes. J Neurochem 2002; 80: 255-261
29. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000; 356: 1627-1631
30. Kabouridis PS, Janzen J, Magee AL, Ley SC. Cholesterol depletion disrupts lipid rafts and modulates the activity of multiple signaling path-ways in T lymphocytes. Eur J Immunol 2000; 30: 954-963
31. Kim HJ, Miyazaki M, Man WC, Ntambi JM. Sterol regulatory element-binding proteins (SREBPs) as regulators of lipid metabolism: polyunsaturated fatty acids oppose cholesterol-mediated induction of SREBP-1 maturation. Ann N Y Acad Sci 2002; 967: 34-42
32. Kirsch C, Eckert GP, Müller WE. Cholesterol attenuates the membrane perturbing properties of β-amyloid peptides. Amyloid 2002; 9: 149-159
33. Kirsch C, Eckert GP, Müller WE. Statin effects on cholesterol micro-domains in brain plasma membranes. Biochem Pharmacol 2003; 65: 843-856
34. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc Natl Acad Sci USA 2001; 98: 5815-5820
35. Komai T, Shigehara E,Tokui T, Koga T, Ishigami M, Kuroiwa C, Horiuchi S. Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture. Biochem Pharmacol 1992; 43: 667-670
36. Koudinov AR, Koudinova NV. Brain cholesterol pathology is the cause of Alzheimer's disease. Clin Med Health Res, 2001; clinmed/ 2 001100 005 ePub available at: http://clinmed.netprints.org/cgi/content/full/2001100005v1
37. Koudinov AR, Koudinova NV. Essential role of cholesterol in synaptic plasticity and neuronal degeneration. FASEB J 2001; 15: 1858-1860
38. Liscum L, Munn NJ. Intracellular cholesterol transport. Biochim Biophys Acta 1999; 1438: 19-37
39. Locatelli S, Lutjohann D, Schmidt HH, Otto C, Beisiegel U, von Bergmann K. Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Arch Neurol 2002; 59: 213-216
40. Lousberg TR, Denham AM, Rasmussen JR. A comparison of clinical outcome studies among cholesterol-lowering agents. Ann Pharmacother 2001; 35: 1599-1607
41. MacDonald AG, Wahle KW, Cossins AR, Behan MK. Temperature, pressure and cholesterol effects on bilayer fluidity; a comparison of pyrene excimer/monomer ratios with the steady-state fluorescence polarization of diphenylhexatriene in liposomes and microsomes. Biochim Biophys Acta 1988; 938: 231-242
42. Maltese WA. Posttranslational modification of proteins by isoprenoids in mammalian cells. Faseb J 1990; 4: 3319-3328
43. Meresse S, Delbart C, Fruchart JC, Cecchelli R. Low-density lipoprotein receptor on endothelium of brain capillaries. J Neurochem 1989; 53: 340-345
44. Petanceska SS, DeRosa S, Olm V, Diaz N, Sharma A, Thomas-Bryant T, Duff K, Pappolla M, Refolo LM. Statin therapy for Alzheimer's disease. Will it work. J Mol Neurosci 2002; 19: 155-161
45. Puglielli L, Konopka G, Pack-Chung E, Ingano LA, Berezovska O, Hyman BT, Chang TY, Tanzi RE, Kovacs DM. Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat Cell Biol 2001; 3: 905-912
46. Refolo LM, Pappolla MA, LaFrancois J, Malester B, Schmidt SD, Thomas-Bryant T, Tint GS, Wang R, Mercken M, Petanceska SS, Duff KE. A Cholesterol-Lowering Drug Reduces beta-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer"s Disease. Neurobiol Dis 2001; 8: 890-899
47. Refolo LM, Pappolla MA, Malester B, LaFrancois J, Schmidt SD, Thomas-Bryant T, Wang R, Tint GS, Sambamurti K, Duff K. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000; 7: 321-331
48. Riddell DR, Christie G, Hussain I, Dingwall C. Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts. Curr Biol 2001; 11: 1288-1293
49. Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, Hartmann T. Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci 2002; 22: 1679-1689
50. Saheki A, Terasaki T, Tamai I, Tsuji A. In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 1994; 11: 305-311
51. Schroeder F, Frolov AA, Murphy EJ, Atshaves BP, Jefferson JR, Pu L, Wood WG, Foxworth WB, Kier AB. Recent advances in membrane cholesterol domain dynamics and intracellular cholesterol trafficking. Proc Soc Exp Biol Med 1996; 213: 150-177
52. Schroeder F, Gallegos AM, Atshaves BP, Storey SM, McIntosh AL, Petrescu AD, Huang H, Starodub O, Chao H, Yang H, Frolov A, Kier AB. Recent advances in membrane microdomains: rafts, caveolae, and intracellular cholesterol trafficking. Exp Biol Med (Maywood) 2001; 226: 873-890
53. Schroeder F, Kier AB, Sweet WD. Role of polyunsaturated fatty acids and lipid peroxidation in LM fibroblast plasma membrane transbilayer structure. Arch Biochem Biophys 1990; 276: 55-64
54. Schroeder F, Nemecz G, Wood WG, Joiner C, Morrot G, Ayraut-Jarrier M, Devaux PF. Transmembrane distribution of sterol in the human erythrocyte. Biochim Biophys Acta 1991; 1066: 183-192
55. nd International Congress on Vascular Dementia, Salzburg, Austria. (Ed by Amos D. Korczyn) Monduzzi Editore. International Proceedings Division, 2002: pp. 147-153
56. Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invets 2002; 110: 597-603
57. Simons K, Ikonen E. How cells handle cholesterol. Science 2000; 290: 1721-1726
58. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998; 95: 6460-6464
59. Skoog I. Vascular aspects in Alzheimer"s disease. J Neural Transm Suppl 2000; 59: 37-43
60. Spector AA. Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain. J Mol Neurosci 2001; 16: 159-165
61. Stulnig TM, Huber J, Leitinger N, Imre EM, Angelisova P, Nowotny P, Waldhausl W. Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem 2001; 276: 37 335-37 340
62. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 1712-1719
63. Tun H, Marlow L, Pinnix I, Kinsey R, Sambamurti K. Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathway. J Mol Neurosci 2002; 19: 31-35
64. Volpe JJ, Goldberg RI, Bhat NR. Cholesterol biosynthesis and its regulation in dissociated cell cultures of fetal rat brain: developmental changes and the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Neurochem 1985; 45: 536-543
65. Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin SG, Golde TE. Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol Dis 2002; 9: 11-23
66. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G. Decreased prevalence of alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57: 1439-1443
67. Wolozin B. A fluid connection: cholesterol and A beta. Proc Natl Acad Sci USA 2001; 98: 5371 -5373
68. Wolozin B. Cholesterol and Alzheimer's disease. Biochem Soc Trans 2002; 30: 525-529
69. Wood WG, Schroeder F, Igbavboa U, Avdulov NA, Chochina SV. Brain membrane cholesterol domains, aging and amyloid beta-peptides. Neurobiol Aging 2002; 23: 685-694
70. Yanagisawa K. Cholesterol and pathological processes in Alzheimer's Disease. J Neurosci Res 2002; 70: 361-366
71. Yao ZX, Papadopoulos V. Function of β-amyloid in cholesterol transport: a lead to neurotoxicity. FASEB J 2002; 16: 1677-1679