Alzheimer's disease: Cholesterol a menace?

Brain Research Bulletin

Volumn 86, Issue 1-2, 2011, Pages 1-12

  Mathew, Anila ^a   Yoshida, Yasuhiko ^a   Maekawa, Toru ^a   Sakthi Kumar, D ^a  

^a TOYO UNIVERSITY   (Japan)

Author keywords

Alzheimer's disease; Amyloid beta; Amyloid precursor protein; Cholesterol

Indexed keywords

ALPHA SECRETASE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E; ATORVASTATIN; CHOLESTEROL; CHOLESTEROL OXIDASE; DESMOSTEROL; DONEPEZIL; GAMMA SECRETASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LANOSTEROL; LIVER X RECEPTOR; MEMBRANE METALLOENDOPEPTIDASE; MEVINOLIN; REACTIVE OXYGEN METABOLITE; SIMVASTATIN; TAU PROTEIN;

ABSENCE OF SIDE EFFECTS; ALZHEIMER DISEASE; AMYLOID PLAQUE; BLOOD BRAIN BARRIER; BRAIN; BRAIN MITOCHONDRION; CARBOXY TERMINAL SEQUENCE; CHOLESTEROL SYNTHESIS; DISEASE ASSOCIATION; ENZYME ACTIVITY; HUMAN; HUNTINGTON CHOREA; NERVE CELL PLASTICITY; NIEMANN PICK DISEASE; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; REVIEW;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; BRAIN; CHOLESTEROL; HUMANS; PLAQUE, AMYLOID; TAU PROTEINS;

EID: 80051599167     PISSN: 03619230     EISSN: 18732747     Source Type: Journal    
DOI: 10.1016/j.brainresbull.2011.06.006     Document Type: Review

References (175)

1. Abad-Rodriguez J., Ledesma M.D., Craessaerts K., Perga S., Medina M., Delacourte A., Dingwall C., De Strooper B., Dotti C.G. Neuronal membrane cholesterol loss enhances amyloid peptide generation. J. Cell Biol. 2004, 167:953-960.
2. Annaert W., De Strooper B. A cell biological perspective on Alzheimer's disease. Annu. Rev. Cell Dev. Biol. 2002, 18:25-51.
3. Arnaud C., Braunersreuther V., Mach F. Toward immunomodulatory and anti-inflammatory properties of statins. Trends Cardiovasc. Med. 2005, 15:202-206.
4. Atamna H., Frey W.H. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 2007, 7:297-310.
5. Avdulov N.A., Chochina S.V., Igbavboa U., Warden C.S., Vassiliev A.V., Wood W.G. Lipid binding to amyloid beta-peptide aggregates: preferential binding of cholesterol as compared with phosphatidylcholine and fatty acids. J. Neurochem. 1997, 69:1746-1752.
6. Baranowski M. Biological role of liver X receptors. J. Physiol. Pharmacol. 2008, 59(Suppl. 7):31-55.
7. Baum L.W. Sex, hormones, and Alzheimer's disease. J. Gerontol. A: Biol. Sci. Med. Sci. 2005, 60:736-743.
8. Bjork B.F., Katzov H., Kehoe P., Fratiglioni L., Winblad B., Prince J.A., Graff C. Positive association between risk for late-onset Alzheimer disease and genetic variation in IDE. Neurobiol. Aging 2007, 28:1374-1380.
9. Bjorkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J. Intern. Med. 2006, 260:493-508.
10. Bohr I.J. Does cholesterol act as a protector of cholinergic projections in Alzheimer's disease?. Lipids Health Dis. 2005, 4:13.
11. Borroni B., Archetti S., Agosti C., Akkawi N., Brambilla C., Caimi L., Caltagirone C., Di Luca M., Padovani A. Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators. Neurobiol. Aging 2004, 25:747-751.
12. Borroni B., Pettenati C., Bordonali T., Akkawi N., Di Luca M., Padovani A. Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease. Neurosci. Lett. 2003, 343:213-215.
13. Borth W. Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J. 1992, 6:3345-3353.
14. Bramlett K.S., Houck K.A., Borchert K.M., Dowless M.S., Kulanthaivel P., Zhang Y., Beyer T.P., Schmidt R., Thomas J.S., Michael L.F., Barr R., Montrose C., Eacho P.I., Cao G., Burris T.P. A natural product ligand of the oxysterol receptor, liver X receptor. J. Pharmacol. Exp. Ther. 2003, 307:291-296.
15. Brookmeyer R., Johnson E., Ziegler-Graham K., Arrighi H.M. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007, 3:186-191.
16. Burns M.P., Igbavboa U., Wang L., Wood W.G., Duff K. Cholesterol distribution, not total levels, correlate with altered amyloid precursor protein processing in statin-treated mice. Neuromol. Med. 2006, 8:319-328.
17. Buxbaum J.D., Geoghagen N.S., Friedhoff L.T. Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J. Alzheimers Dis. 2001, 3:221-229.
18. Cao G., Bales K.R., DeMattos R.B., Paul S.M. Liver X receptor-mediated gene regulation and cholesterol homeostasis in brain: relevance to Alzheimer's disease therapeutics. Curr Alzheimer Res. 2007, 4:179-184.
19. Cao G., Liang Y., Broderick C.L., Oldham B.A., Beyer T.P., Schmidt R.J., Zhang Y., Stayrook K.R., Suen C., Otto K.A., Miller A.R., Dai J., Foxworthy P., Gao H., Ryan T.P., Jiang X.C., Burris T.P., Eacho P.I., Etgen G.J. Antidiabetic action of a liver x receptor agonist mediated by inhibition of hepatic gluconeogenesis. J. Biol. Chem. 2003, 278:1131-1136.
20. Carrillo M.C., Blackwell A., Hampel H., Lindborg J., Sperling R., Schenk D., Sevigny J.J., Ferris S., Bennett D.A., Craft S., Hsu T., Klunk W. Early risk assessment for Alzheimer's disease. Alzheimers Dement. 2009, 5:182-196.
21. Carson J.A., Turner A.J. Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?. J. Neurochem. 2002, 81:1-8.
22. Chen X., Ghribi O., Geiger J.D. Rabbits fed cholesterol-enriched diets exhibit pathological features of inclusion body myositis. Am J Physiol Regul Integr Comp Physiol. 2008, 294:R829-R835.
23. Colell A., Fernandez A., Fernandez-Checa J.C. Mitochondria, cholesterol and amyloid beta peptide: a dangerous trio in Alzheimer disease. J. Bioenerg. Biomembr. 2009, 41:417-423.
24. Combarros O., Infante J., Llorca J., Berciano J. Genetic association of CYP46 and risk for Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 2004, 18:257-260.
25. Corbo R.M., Gambina G., Ulizzi L., Moretto G., Scacchi R. Genetic variation of CYP19 (aromatase) gene influences age at onset of Alzheimer's disease in women. Dement. Geriatr. Cogn. Disord. 2009, 27:513-518.
26. Crameri A., Biondi E., Kuehnle K., Lutjohann D., Thelen K.M., Perga S., Dotti C.G., Nitsch R.M., Ledesma M.D., Mohajeri M.H. The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. EMBO J. 2006, 25:432-443.
27. Cui R., Iso H., Toyoshima H., Date C., Yamamoto A., Kikuchi S., Kondo T., Watanabe Y., Koizumi A., Inaba Y., Tamakoshi A. Serum total cholesterol levels and risk of mortality from stroke and coronary heart disease in Japanese: the JACC study. Atherosclerosis 2007, 194:415-420.
28. Cummings J.L. Alzheimer's disease. N. Engl. J. Med. 2004, 351:56-67.
29. Cutler R.G., Kelly J., Storie K., Pedersen W.A., Tammara A., Hatanpaa K., Troncoso J.C., Mattson M.P. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:2070-2075.
30. Dante S., Hauss T., Dencher N.A. Cholesterol inhibits the insertion of the Alzheimer's peptide Abeta(25-35) in lipid bilayers. Eur. Biophys. J. 2006, 35:523-531.
31. de la Torre J.C. Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol. 2004, 3:184-190.
32. Delvecchio C.J., Bilan P., Radford K., Stephen J., Trigatti B.L., Cox G., Parameswaran K., Capone J.P. Liver X receptor stimulates cholesterol efflux and inhibits expression of proinflammatory mediators in human airway smooth muscle cells. Mol. Endocrinol. 2007, 21:1324-1334.
33. Dietschy J.M. Regulation of cholesterol metabolism in man and in other species. Klin. Wochenschr. 1984, 62:338-345.
34. Donahue J.E., Flaherty S.L., Johanson C.E., Duncan J.A., Silverberg G.D., Miller M.C., Tavares R., Yang W., Wu Q., Sabo E., Hovanesian V., Stopa E.G. RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease. Acta Neuropathol. 2006, 112:405-415.
35. Eckert G.P., Kirsch C., Leutz S., Wood W.G., Muller W.E. Cholesterol modulates amyloid beta-peptide's membrane interactions. Pharmacopsychiatry 2003, 36(Suppl. 2):S136-S143.
36. Edland S.D., Wavrant-De Vriese F., Compton D., Smith G.E., Ivnik R., Boeve B.F., Tangalos E.G., Petersen R.C. Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease: evidence of effect modification by apolipoprotein E (APOE). Neurosci. Lett. 2003, 345:21-24.
37. Elshourbagy N.A., Liao W.S., Mahley R.W., Taylor J.M. Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc. Natl. Acad. Sci. U. S. A. 1985, 82:203-207.
38. Farooqui A.A., Ong W.Y., Farooqui T. Lipid mediators in the nucleus: their potential contribution to Alzheimer's disease. Biochim. Biophys. Acta 2010, 1801:906-916.
39. Fassbender K., Simons M., Bergmann C., Stroick M., Lutjohann 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. U. S. A. 2001, 98:5856-5861.
40. Feldman H.H., Doody R.S., Kivipelto M., Sparks D.L., Waters D.D., Jones R.W., Schwam E., Schindler R., Hey-Hadavi J., DeMicco D.A., Breazna A. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 2010, 74:956-964.
41. Fillit H. Atorvastatin does not slow cognitive decline in patients with mild to moderate probable Alzheimer's disease who are taking donepezil. Evid. Based Ment. Health 2010.
42. Frears E.R., Stephens D.J., Walters C.E., Davies H., Austen B.M. The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 1999, 10:1699-1705.
43. Ghribi O., Larsen B., Schrag M., Herman M.M. High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp. Neurol. 2006, 200:460-467.
44. Gorelick P.B. Risk factors for vascular dementia and Alzheimer disease. Stroke 2004, 35:2620-2622.
45. Graeber M.B., Mehraein P. Reanalysis of the first case of Alzheimer's disease. Eur. Arch. Psychiatry Clin. Neurosci. 1999, 249(Suppl. 3):10-13.
46. Green R.C., McNagny S.E., Jayakumar P., Cupples L.A., Benke K., Farrer L.A. Statin use and the risk of Alzheimer's disease: the MIRAGE study. Alzheimers Dement. 2006, 2:96-103.
47. Haass C., Schlossmacher M.G., Hung A.Y., Vigo-Pelfrey C., Mellon A., Ostaszewski B.L., Lieberburg I., Koo E.H., Schenk D., Teplow D.B., et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 1992, 359:322-325.
48. Halford R.W., Russell D.W. Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimer's disease, but does extend lifespan. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:3502-3506.
49. Harris J.R. Cholesterol binding to amyloid-beta fibrils: a TEM study. Micron 2008, 39:1192-1196.
50. Harris-White M.E., Frautschy S.A. Low density lipoprotein receptor-related proteins (LRPs), Alzheimer's and cognition. Curr. Drug Targets CNS Neurol. Disord. 2005, 4:469-480.
51. Hartmann T. Cholesterol, Abeta and Alzheimer's disease. Trends Neurosci. 2001, 24:S45-S48.
52. Hartmann T., Kuchenbecker J., Grimm M.O. Alzheimer's disease: the lipid connection. J. Neurochem. 2007, 103(Suppl. 1):159-170.
53. Hauptmann S., Keil U., Scherping I., Bonert A., Eckert A., Muller W.E. Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease. Exp. Gerontol. 2006, 41:668-673.
54. Hebert L.E., Scherr P.A., McCann J.J., Beckett L.A., Evans D.A. Is the risk of developing Alzheimer's disease greater for women than for men?. Am. J. Epidemiol. 2001, 153:132-136.
55. Heverin M., Bogdanovic N., Lutjohann D., Bayer T., Pikuleva I., Bretillon L., Diczfalusy U., Winblad B., Bjorkhem I. Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J. Lipid Res. 2004, 45:186-193.
56. Hirsch-Reinshagen V., Burgess B.L., Wellington C.L. Why lipids are important for Alzheimer disease?. Mol. Cell. Biochem. 2009, 326:121-129.
57. Hodges J.R. Alzheimer's centennial legacy: origins, landmarks and the current status of knowledge concerning cognitive aspects. Brain 2006, 129:2811-2822.
58. Hu G., Antikainen R., Jousilahti P., Kivipelto M., Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology 2008, 70:1972-1979.
59. Huttunen H.J., Kovacs D.M. ACAT as a drug target for Alzheimer's disease. Neurodegener Dis. 2008, 5:212-214.
60. Janowski B.A., Willy P.J., Devi T.R., Falck J.R., Mangelsdorf D.J. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 1996, 383:728-731.
61. Jaya Prasanthi R.P., Schommer E., Thomasson S., Thompson A., Feist G., Ghribi O. Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. Mech. Ageing Dev. 2008, 129:649-655.
62. Jellinger K.A. Alzheimer 100 - highlights in the history of Alzheimer research. J. Neural Transm. 2006, 113:1603-1623.
63. Jick H., Zornberg G.L., Jick S.S., Seshadri S., Drachman D.A. Statins and the risk of dementia. Lancet 2000, 356:1627-1631.
64. Johnson G.V., Stoothoff W.H. Tau phosphorylation in neuronal cell function and dysfunction. J. Cell Sci. 2004, 117:5721-5729.
65. Joseph S.B., Castrillo A., Laffitte B.A., Mangelsdorf D.J., Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med. 2003, 9:213-219.
66. Kern A., Behl C. The unsolved relationship of brain aging and late-onset Alzheimer disease. Biochim. Biophys. Acta 2009, 1790:1124-1132.
67. Kimberly W.T., Zheng J.B., Guenette S.Y., Selkoe D.J. The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J. Biol. Chem. 2001, 276:40288-40292.
68. Kinosian B., Glick H., Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann. Intern. Med. 1994, 121:641-647.
69. Kivipelto M., Helkala E.L., Laakso M.P., Hanninen T., Hallikainen M., Alhainen K., Soininen H., Tuomilehto J., Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001, 322:1447-1451.
70. Kivipelto M., Solomon A., Blennow K., Olsson A.G., Winblad B. The new cholesterol controversy - a little bit of history repeating?. Acta Neurol. Scand. 2006, 185(Suppl.):1-2.
71. Koldamova R.P., Lefterov I.M., Staufenbiel M., Wolfe D., Huang S., Glorioso J.C., Walter M., Roth M.G., Lazo J.S. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J. Biol. Chem. 2005, 280:4079-4088.
72. Kolsch H., Heun R., Jessen F., Popp J., Hentschel F., Maier W., Lutjohann D. Alterations of cholesterol precursor levels in Alzheimer's disease. Biochim. Biophys. Acta 2010, 1801:945-950.
73. Korovaitseva G.I., Premkumar S., Grigorenko A., Molyaka Y., Galimbet V., Selezneva N., Gavrilova S.I., Farrer L.A., Rogaev E.I. Alpha-2 macroglobulin gene in early- and late-onset Alzheimer disease. Neurosci. Lett. 1999, 271:129-131.
74. Koudinov A.R., Berezov T.T. Alzheimer's amyloid-beta (A beta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol. Exp. (Wars) 2004, 64:71-79.
75. Koudinov A.R., Koudinova N.V. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. 2001, 15:1858-1860.
76. Koudinov A.R., Koudinova N.V. Cholesterol, synaptic function and Alzheimer's disease. Pharmacopsychiatry 2003, 36(Suppl. 2):S107-S112.
77. Koudinov A.R., Koudinova N.V. Cholesterol homeostasis failure as a unifying cause of synaptic degeneration. J. Neurol. Sci. 2005, 229-230:233-240.
78. Kovacs D.M. alpha2-macroglobulin in late-onset Alzheimer's disease. Exp. Gerontol. 2000, 35:473-479.
79. Kraemer H.C., Taylor J.L., Tinklenberg J.R., Yesavage J.A. The stages of Alzheimer's disease: a reappraisal. Dement. Geriatr. Cogn. Disord. 1998, 9:299-308.
80. Lanctot K.L., Hsiung G.Y., Feldman H.H., Masoud S.T., Sham L., Herrmann N. Assessing the validity of deriving clinical dementia rating (CDR) global scores from independently-obtained functional rating scale (FRS) scores in vascular dementia with and without Alzheimer's disease. Int. J. Geriatr. Psychiatry 2009, 24:1174-1176.
81. Lerner A.J. Women and Alzheimer's disease. J. Clin. Endocrinol. Metab. 1999, 84:1830-1834.
82. Lin M.C., Kagan B.L. Electrophysiologic properties of channels induced by Abeta 25-35 in planar lipid bilayers. Peptides 2002, 23:1215-1228.
83. Liu J.P., Tang Y., Zhou S., Toh B.H., McLean C., Li H. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol. Cell. Neurosci. 2010, 43:33-42.
84. Luo Y., Tall A.R. Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J. Clin. Invest. 2000, 105:513-520.
85. Lutjohann D., Brzezinka A., Barth E., Abramowski D., Staufenbiel M., von Bergmann K., Beyreuther K., Multhaup G., Bayer T.A. Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J. Lipid Res. 2002, 43:1078-1085.
86. Mandelkow E.M., Mandelkow E. Tau in Alzheimer's disease. Trends Cell Biol. 1998, 8:425-427.
87. Martin E.R., Lai E.H., Gilbert J.R., Rogala A.R., Afshari A.J., Riley J., Finch K.L., Stevens J.F., Livak K.J., Slotterbeck B.D., Slifer S.H., Warren L.L., Conneally P.M., Schmechel D.E., Purvis I., Pericak-Vance M.A., Roses A.D., Vance J.M. SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. Am. J. Hum. Genet. 2000, 67:383-394.
88. Martin M., Dotti C.G., Ledesma M.D. Brain cholesterol in normal and pathological aging. Biochim. Biophys. Acta 2010, 1801:934-944.
89. Maruszak A., Zekanowski C. Mitochondrial dysfunction and Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2011, 35:320-330.
90. Mason R.P., Shoemaker W.J., Shajenko L., Chambers T.E., Herbette L.G. Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol. Neurobiol. Aging 1992, 13:413-419.
91. Mattson M.P. Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol. 2000, 1:120-129.
92. Maurer K., Volk S., Gerbaldo H. Auguste D and Alzheimer's disease. Lancet 1997, 349:1546-1549.
93. Merlini G., Bellotti V. Molecular mechanisms of amyloidosis. N. Engl. J. Med. 2003, 349:583-596.
94. Meske V., Albert F., Richter D., Schwarze J., Ohm T.G. Blockade of HMG-CoA reductase activity causes changes in microtubule-stabilizing protein tau via suppression of geranylgeranylpyrophosphate formation: implications for Alzheimer's disease. Eur. J. Neurosci. 2003, 17:93-102.
95. Miller L.J., Chacko R. The role of cholesterol and statins in Alzheimer's disease. Ann Pharmacother. 2004, 38:91-98.
96. Muller W.E., Eckert A., Kurz C., Eckert G.P., Leuner K. Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer's disease - therapeutic aspects. Mol. Neurobiol. 2010, 41:159-171.
97. Nawarskas J.J. HMG-CoA reductase inhibitors and coenzyme Q10. Cardiol. Rev. 2005, 13:76-79.
98. Nunan J., Small D.H. Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett. 2000, 483:6-10.
99. Ojaimi J., Byrne E. Mitochondrial function and Alzheimer's disease. Biol. Signals Recept. 2001, 10:254-262.
100. Papassotiropoulos A., Lambert J.C., Wavrant-De Vrieze F., Wollmer M.A., von der Kammer H., Streffer J.R., Maddalena A., Huynh K.D., Wolleb S., Lutjohann D., Schneider B., Thal D.R., Grimaldi L.M., Tsolaki M., Kapaki E., Ravid R., Konietzko U., Hegi T., Pasch T., Jung H., Braak H., Amouyel P., Rogaev E.I., Hardy J., Hock C., Nitsch R.M. Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease. Neurodegener. Dis. 2005, 2:233-241.
101. Papassotiropoulos A., Streffer J.R., Tsolaki M., Schmid S., Thal D., Nicosia F., Iakovidou V., Maddalena A., Lutjohann D., Ghebremedhin E., Hegi T., Pasch T., Traxler M., Bruhl A., Benussi L., Binetti G., Braak H., Nitsch R.M., Hock C. Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism. Arch. Neurol. 2003, 60:29-35.
102. Park I.H., Hwang E.M., Hong H.S., Boo J.H., Oh S.S., Lee J., Jung M.W., Bang O.Y., Kim S.U., Mook-Jung I. Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol. Aging 2003, 24:637-643.
103. Pentchev P.G., Comly M.E., Kruth H.S., Vanier M.T., Wenger D.A., Patel S., Brady R.O. A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc. Natl. Acad. Sci. U. S. A. 1985, 82:8247-8251.
104. Pfrieger F.W. Role of cholesterol in synapse formation and function. Biochim. Biophys. Acta 2003, 1610:271-280.
105. Puglielli L., Ellis B.C., Ingano L.A., Kovacs D.M. Role of acyl-coenzyme A: cholesterol acyltransferase activity in the processing of the amyloid precursor protein. J. Mol. Neurosci. 2004, 24:93-96.
106. Puglielli L., Friedlich A.L., Setchell K.D., Nagano S., Opazo C., Cherny R.A., Barnham K.J., Wade J.D., Melov S., Kovacs D.M., Bush A.I. Alzheimer disease beta-amyloid activity mimics cholesterol oxidase. J. Clin. Invest. 2005, 115:2556-2563.
107. Puglielli L., Konopka G., Pack-Chung E., Ingano L.A., Berezovska O., Hyman B.T., Chang T.Y., Tanzi R.E., Kovacs D.M. Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat. Cell Biol. 2001, 3:905-912.
108. Puglielli L., Tanzi R.E., Kovacs D.M. Alzheimer's disease: the cholesterol connection. Nat. Neurosci. 2003, 6:345-351.
109. Rahman A., Akterin S., Flores-Morales A., Crisby M., Kivipelto M., Schultzberg M., Cedazo-Minguez A. High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice. FEBS Lett. 2005, 579:6411-6416.
110. Reddy P.H., Beal M.F. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med. 2008, 14:45-53.
111. Refolo L.M., Malester B., LaFrancois J., Bryant-Thomas T., Wang R., Tint G.S., Sambamurti K., Duff K., Pappolla M.A. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol. Dis. 2000, 7:321-331.
112. Refolo L.M., Pappolla M.A., LaFrancois J., Malester B., Schmidt S.D., Thomas-Bryant T., Tint G.S., Wang R., Mercken M., Petanceska S.S., Duff K.E. A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol. Dis. 2001, 8:890-899.
113. Reid P.C., Urano Y., Kodama T., Hamakubo T. Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. J. Cell. Mol. Med. 2007, 11:383-392.
114. Reisberg B., Ferris S.H., de Leon M.J., Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am. J. Psychiatry 1982, 139:1136-1139.
115. Reisberg B., Schneider L., Doody R., Anand R., Feldman H., Haraguchi H., Kumar R., Lucca U., Mangone C.A., Mohr E., Morris J.C., Rogers S., Sawada T. Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. Alzheimer Dis. Assoc. Disord. 1997, 11(Suppl. 3):8-18.
116. Reiss A.B. Cholesterol and apolipoprotein E in Alzheimer's disease. Am. J. Alzheimers Dis. Other Demen. 2005, 20:91-96.
117. Reiss A.B., Siller K.A., Rahman M.M., Chan E.S., Ghiso J., de Leon M.J. Cholesterol in neurologic disorders of the elderly: stroke and Alzheimer's disease. Neurobiol. Aging 2004, 25:977-989.
118. Repa J.J., Mangelsdorf D.J. The liver X receptor gene team: potential new players in atherosclerosis. Nat. Med. 2002, 8:1243-1248.
119. Riddell D.R., Zhou H., Comery T.A., Kouranova E., Lo C.F., Warwick H.K., Ring R.H., Kirksey Y., Aschmies S., Xu J., Kubek K., Hirst W.D., Gonzales C., Chen Y., Murphy E., Leonard S., Vasylyev D., Oganesian A., Martone R.L., Pangalos M.N., Reinhart P.H., Jacobsen J.S. The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Mol. Cell. Neurosci. 2007, 34:621-628.
120. Riemenschneider M., Mahmoodzadeh S., Eisele T., Klopp N., Schwarz S., Wagenpfeil S., Diehl J., Mueller U., Foerstl H., Illig T., Kurz A. Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease. Neurobiol. Aging 2004, 25:1305-1308.
121. Rockwood K., Kirkland S., Hogan D.B., MacKnight C., Merry H., Verreault R., Wolfson C., McDowell I. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch. Neurol. 2002, 59:223-227.
122. Rodriguez-Rodriguez E., Mateo I., Infante J., Llorca J., Garcia-Gorostiaga I., Vazquez-Higuera J.L., Sanchez-Juan P., Berciano J., Combarros O. Interaction between HMGCR and ABCA1 cholesterol-related genes modulates Alzheimer's disease risk. Brain Res. 2009, 1280:166-171.
123. Rojo L., Sjoberg M.K., Hernandez P., Zambrano C., Maccioni R.B. Roles of cholesterol and lipids in the etiopathogenesis of Alzheimer's disease. J. Biomed. Biotechnol. 2006, 2006:73976.
124. Roses A.D. Apolipoprotein E and Alzheimer's disease. A rapidly expanding field with medical and epidemiological consequences. Ann. N. Y. Acad. Sci. 1996, 802:50-57.
125. Roses A.D., Lutz M.W., Amrine-Madsen H., Saunders A.M., Crenshaw D.G., Sundseth S.S., Huentelman M.J., Welsh-Bohmer K.A., Reiman E.M. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenom. J. 2009.
126. Sambamurti K., Greig N.H., Lahiri D.K. Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer's disease. Neuromol. Med. 2002, 1:1-31.
127. Sanossian N., Saver J.L., Kim D., Razinia T., Ovbiagele B. Do high-density lipoprotein cholesterol levels influence stroke severity?. J. Stroke Cerebrovasc. Dis. 2006, 15:187-189.
128. Sato N., Ueki A., Ueno H., Shinjo H., Morita Y. IDE gene polymorphism influences on BPSD in mild dementia of Alzheimer's Type. Curr Gerontol Geriatr Res. 2008, 759-858.
129. Selkoe D.J. Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 2001, 81:741-766.
130. Seol W., Choi H.S., Moore D.D. Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol. Endocrinol. 1995, 9:72-85.
131. Shibata N., Kawarai T., Lee J.H., Lee H.S., Shibata E., Sato C., Liang Y., Duara R., Mayeux R.P., St George-Hyslop P.H., Rogaeva E. Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease. Neurosci. Lett. 2006, 391:142-146.
132. Shie F.S., Jin L.W., Cook D.G., Leverenz J.B., LeBoeuf R.C. Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice. Neuroreport 2002, 13:455-459.
133. Shinar D.M., Endo N., Rutledge S.J., Vogel R., Rodan G.A., Schmidt A. NER, a new member of the gene family encoding the human steroid hormone nuclear receptor. Gene 1994, 147:273-276.
134. Shobab L.A., Hsiung G.Y., Feldman H.H. Cholesterol in Alzheimer's disease. Lancet Neurol. 2005, 4:841-852.
135. Simons M., Keller P., De Strooper B., Beyreuther K., Dotti C.G., Simons K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:6460-6464.
136. Sjogren M., Mielke M., Gustafson D., Zandi P., Skoog I. Cholesterol and Alzheimer's disease - is there a relation?. Mech. Ageing Dev. 2006, 127:138-147.
137. Small D.H., Mok S.S., Bornstein J.C. Alzheimer's disease and Abeta toxicity: from top to bottom. Nat. Rev. Neurosci. 2001, 2:595-598.
138. Sparks D.L., Kuo Y.M., Roher A., Martin T., Lukas R.J. Alterations of Alzheimer's disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations. Ann. N. Y. Acad. Sci. 2000, 903:335-344.
139. Sparks D.L., Scheff S.W., Hunsaker J.C., Liu H., Landers T., Gross D.R. Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp. Neurol. 1994, 126:88-94.
140. Stulnig T.M., Steffensen K.R., Gao H., Reimers M., Dahlman-Wright K., Schuster G.U., Gustafsson J.A. Novel roles of liver X receptors exposed by gene expression profiling in liver and adipose tissue. Mol. Pharmacol. 2002, 62:1299-1305.
141. Surugiu-Warnmark I., Warnmark A., Toresson G., Gustafsson J.A., Bulow L. Selection of DNA aptamers against rat liver X receptors. Biochem. Biophys. Res. Commun. 2005, 332:512-517.
142. Takei N., Miyashita A., Tsukie T., Arai H., Asada T., Imagawa M., Shoji M., Higuchi S., Urakami K., Kimura H., Kakita A., Takahashi H., Tsuji S., Kanazawa I., Ihara Y., Odani S., Kuwano R. Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 2009, 93:441-448.
143. Tangirala R.K., Bischoff E.D., Joseph S.B., Wagner B.L., Walczak R., Laffitte B.A., Daige C.L., Thomas D., Heyman R.A., Mangelsdorf D.J., Wang X., Lusis A.J., Tontonoz P., Schulman I.G. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:11896-11901.
144. Thinakaran G., Koo E.H. Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem. 2008, 283:29615-29619.
145. Tiraboschi P., Hansen L.A., Thal L.J., Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology 2004, 62:1984-1989.
146. Tontonoz P., Mangelsdorf D.J. Liver X receptor signaling pathways in cardiovascular disease. Mol. Endocrinol. 2003, 17:985-993.
147. Tsui-Pierchala B.A., Encinas M., Milbrandt J., Johnson E.M. Lipid rafts in neuronal signaling and function. Trends Neurosci. 2002, 25:412-417.
148. Valenza M., Cattaneo E. Cholesterol dysfunction in neurodegenerative diseases: is Huntington's disease in the list?. Prog. Neurobiol. 2006, 80:165-176.
149. Valenza M., Rigamonti D., Goffredo D., Zuccato C., Fenu S., Jamot L., Strand A., Tarditi A., Woodman B., Racchi M., Mariotti C., Di Donato S., Corsini A., Bates G., Pruss R., Olson J.M., Sipione S., Tartari M., Cattaneo E. Dysfunction of the cholesterol biosynthetic pathway in Huntington's disease. J. Neurosci. 2005, 25:9932-9939.
150. van der Burg J.M., Bjorkqvist M., Brundin P. Beyond the brain: widespread pathology in Huntington's disease. Lancet Neurol. 2009, 8:765-774.
151. van der Most P.J., Dolga A.M., Nijholt I.M., Luiten P.G., Eisel U.L. Statins: mechanisms of neuroprotection. Prog. Neurobiol. 2009, 88:64-75.
152. von Rotz R.C., Kohli B.M., Bosset J., Meier M., Suzuki T., Nitsch R.M., Konietzko U. The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor. J. Cell Sci. 2004, 117:4435-4448.
153. Wahrle S., Das P., Nyborg A.C., McLendon C., Shoji M., Kawarabayashi T., Younkin L.H., Younkin S.G., Golde T.E. Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol. Dis. 2002, 9:11-23.
154. Walter J., Kaether C., Steiner H., Haass C. The cell biology of Alzheimer's disease: uncovering the secrets of secretases. Curr. Opin. Neurobiol. 2001, 11:585-590.
155. Wang F., Jia J. Polymorphisms of cholesterol metabolism genes CYP46 and ABCA1 and the risk of sporadic Alzheimer's disease in Chinese. Brain Res. 2007, 1147:34-38.
156. Wang Y.Y., Dahle M.K., Steffensen K.R., Reinholt F.P., Collins J.L., Thiemermann C., Aasen A.O., Gustafsson J.A., Wang J.E. Liver X receptor agonist GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages. Shock 2009, 32:548-553.
157. Wavrant-De Vrieze F., Compton D., Womick M., Arepalli S., Adighibe O., Li L., Perez-Tur J., Hardy J. ABCA1 polymorphisms and Alzheimer's disease. Neurosci. Lett. 2007, 416:180-183.
158. Wilquet V., De Strooper B. Amyloid-beta precursor protein processing in neurodegeneration. Curr. Opin. Neurobiol. 2004, 14:582-588.
159. Wisniewski T., Ghiso J., Frangione B. Biology of A beta amyloid in Alzheimer's disease. Neurobiol. Dis. 1997, 4:313-328.
160. Wojcicka G., Jamroz-Wisniewska A., Horoszewicz K., Beltowski J. Liver X receptors (LXRs). Part I: structure, function, regulation of activity, and role in lipid metabolism. Postepy Hig. Med. Dosw. (Online) 2007, 61:736-759.
161. Wolozin B. A fluid connection: cholesterol and Abeta. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:5371-5373.
162. Wolozin B. Cholesterol and the biology of Alzheimer's disease. Neuron 2004, 41:7-10.
163. Wood W.G., Schroeder F., Igbavboa U., Avdulov N.A., Chochina S.V. Brain membrane cholesterol domains, aging and amyloid beta-peptides. Neurobiol. Aging 2002, 23:685-694.
164. Yao Z.X, Papadopoulos V. Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity. FASEB J. 2002, 16:1677-1679.
165. Yip C.M., Elton E.A., Darabie A.A., Morrison M.R., McLaurin J. Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and neurotoxicity. J. Mol. Biol. 2001, 311:723-734.
166. Yu L., York J., von Bergmann K., Lutjohann D., Cohen J.C., Hobbs H.H. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J. Biol. Chem. 2003, 278:15565-15570.
167. Zandi P.P., Sparks D.L., Khachaturian A.S., Tschanz J., Norton M., Steinberg M., Welsh-Bohmer K.A., Breitner J.C. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch. Gen. Psychiatry 2005, 62:217-224.
168. Zanetti O., Solerte S.B., Cantoni F. Life expectancy in Alzheimer's disease (AD). Arch. Gerontol. Geriatr. 2009, 49(Suppl. 1):237-243.
169. Zhang Y., Zhang X., Chen L., Wu J., Su D., Lu W.J., Hwang M.T., Yang G., Li S., Wei M., Davis L., Breyer M.D., Guan Y. Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule. Am. J. Physiol. Renal Physiol. 2006, 290:F1065-F1073.
170. Zheng H., Koo E.H. The amyloid precursor protein: beyond amyloid. Mol Neurodegener. 2006, 1:5.
171. Zhou Y., Richardson J.S. Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and cytotoxicity. Neuroreport 1996, 7:2487-2490.
172. Zhu X., Su B., Wang X., Smith M.A., Perry G. Causes of oxidative stress in Alzheimer disease. Cell. Mol. Life Sci. 2007, 64:2202-2210.
173. Zlokovic B.V. Clearing amyloid through the blood-brain barrier. J. Neurochem. 2004, 89:807-811.
174. Zlokovic B.V. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci. 2005, 28:202-208.
175. Zou K., Kim D., Kakio A., Byun K., Gong J.S., Kim J., Kim M., Sawamura N., Nishimoto S., Matsuzaki K., Lee B., Yanagisawa K., Michikawa M. Amyloid beta-protein (Abeta)1-40 protects neurons from damage induced by Abeta1-42 in culture and in rat brain. J. Neurochem. 2003, 87:609-619.