Cholesterol and statins in Alzheimer's disease: Current controversies

Experimental Neurology

Volumn 223, Issue 2, 2010, Pages 282-293

  Fonseca, Ana Catarina R G ^a   Resende, Rosa ^a   Oliveira, Catarina R ^a,b   Pereira, Cláudia M F ^a,b  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Alzheimer's disease; Amyloid beta; APP processing; Cholesterol synthesis; Isoprenoids; Lipid rafts; Statins

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; ATORVASTATIN; BETA SECRETASE; CERIVASTATIN; CHOLESTEROL; COMPACTIN; FLUINDOSTATIN; GAMMA SECRETASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOPRENOID; MEVINOLIN; PITAVASTATIN; PRAVASTATIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; ROSUVASTATIN; SIMVASTATIN;

ALZHEIMER DISEASE; ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; DEGENERATIVE DISEASE; DRUG PROTEIN BINDING; HUMAN; IMMUNOMODULATION; MOLECULAR MECHANICS; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN PROCESSING; PROTEIN SYNTHESIS INHIBITION; REVIEW;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; CHOLESTEROL; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MEMBRANE MICRODOMAINS; NERVE DEGENERATION;

EID: 77952583554     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2009.09.013     Document Type: Review

References (220)

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. Akasofu S., Kimura M., Kosasa T., Sawada K., Ogura H. Study of neuroprotection of donepezil, a therapy for Alzheimer's disease. Chem.-Biol. Interact. 2008, 175:222-226.
3. Arispe N., Doh M. Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AβP (1-40) and (1-42) peptides. FASEB J. 2002, 16:1526-1536.
4. Bate C., Williams A. Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A2 by Aβ1-42. Neuropharmacology 2007, 53:222-231.
5. Beeri M.S., Rapp M., Silverman J.M., Schmeidler J., Grossman H.T., Fallon J.T., Purohit D.P., Perl D.P., Siddiqui A., Lesser G., Rosendorff C., Haroutunian V. Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers. Neurology 2006, 66:1399-1404.
6. Bi X., Baudry M., Liu J., Yao Y., Fu L., Brucher F., Lynch G. Inhibition of geranylgeranylation mediates the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors on microglia. J. Biol. Chem. 2004, 279:48238-48245.
7. Bieschke J., Zhang Q., Powers E.T., Lerner R.A., Kelly J.W. Oxidative metabolites accelerate Alzheimer's amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation. Biochemistry 2005, 44:4977-4983.
8. Blanco-Colio L.M., Villa A., Ortego M., Hernández-Presa M.A., Pascual A., Plaza J.J., Egido J. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. Atherosclerosis 2002, 161:17-26.
9. Bodovitz S., Klein W.L. Cholesterol modulates β-secretase cleavage of amyloid precursor protein. J. Biol. Chem. 1996, 271:4436-4440.
10. Borronia B., Archettib S., Agostia C., Akkawia N., Brambillaa C., Caimic L., Caltagironed C., Lucae M.D., 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.
11. Bösel J., Gandor F., Harms C., Synowitz M., Harms U., Djoufack P.C., Megow D., Dirnagl U., Hörtnagl H., Fink K.B., Endres M. Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J. Neurochem. 2005, 92:1386-1398.
12. Burns M., Duff K. Use of in vivo models to study the role of cholesterol in the etiology of Alzheimer's disease. Neurochem. Res. 2003, 21:979-986.
13. Burns M., Gaynor K., Olm V., Mercken M., LaFrancois J., Wang L., Mathews P.M., Noble W., Matsuoka Y., Duff K. Presenilin redistribution associated with aberrant cholesterol transport enhances β-amyloid production in vivo. J. Neurosci. 2003, 23:5645-5649.
14. 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.
15. Busciglio J., Gabuzda D.H., Matsudaira P., Yankner B. Generation of, β-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc. Natl. Acad. Sci. U. S. A. 1993, 90:2092-2096.
16. Buxbaum J.D., Liu K.-N., Luo Y., Slack J.L., Stocking K.L., Peschon J.J., Johnson R.S., Castner B.J., Cerretti D.P., Black R.A. Evidence that tumor necrosis factor a converting enzyme is involved in regulated β-secretase cleavage of the Alzheimer amyloid protein precursor. J. Biol. Chem. 1998, 273:27765-27767.
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. Alzheimer's Dis. 2001, 3:221-229.
18. Buxbaum J.D., Cullen E.I., Friedhoff L.T. Pharmacological concentrations of the HMG-CoA reductase inhibitor lovastatin decrease the formation of the Alzheimer β-amyloid peptide in vitro and in patients. Front. Biosci. 2002, 7:a50-59.
19. Calleros L., Lasa M., Rodríguez-Álvarez F.J., Toro M.J., Chiloeches A. RhoA and p38 MAPK mediate apoptosis induced by cellular cholesterol depletion. Apoptosis 2006, 11:1161-1173.
20. Casserly I., Topol E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet 2004, 363:1139-1146.
21. Cerezo-Guisado M.I., Garcia-Marin L.J., Lorenzo M.J., Bragado M.J. Lovastatin inhibits the growth and survival pathway of phosphoinositide 3-kinase/protein kinase B in immortalized rat brain neuroblasts. J. Neurochem. 2005, 94:1277-1287.
22. Chen J., Zhang Z.G., Li Y., Wang Y., Wang L., Jiang H., Zhang C., Lu M., Katakowski M., Feldkamp C.S., Chopp M. Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann. Neurol. 2003, 53:743-751.
23. Chong P.H., Seeger J.D., Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am. J. Med. 2001, 111:390-400.
24. Cibičková L., Palička V., Cibiček N., Čermáková E., Mičuda S., Bartošová L., Jun D. Differential effects of statins and alendronate on cholinesterases in serum and brain of rats. Physiol. Res. 2007, 56:765-770.
25. Clarke R.M., O'Connell F., Lyons A., Lynch M.A. The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-β1-42 in the rat hippocampus in vivo. Neuropharmacology 2007, 52:136-145.
26. Clarke R.M., Lyons A., O'Connell F., Deighan B.F., Barry C.E., Anyakoha N.G., Nicolaou A., Lynch M.A. A pivotal role for interleukin-4 in atorvastatin-associated neuroprotection in rat brain. J. Biol. Chem. 2008, 283:1808-1817.
27. Cole S.L., Grudzien A., Manhart I.O., Kelly B.L., Oakley H., Vassar R. Statins cause intracellular accumulation of amyloid precursor protein, β-secretase-cleaved fragments, and amyloid β-peptide via an isoprenoid-dependent mechanism. J. Biol. Chem. 2005, 280:18755-18770.
28. Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E., Gaskell P.C., Small G.W., Roses A.D., Haines J.L., Pericak-Vance M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993, 261:921-923.
29. Cordle A., Landreth G. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate β-amyloid-induced microglial inflammatory responses. J. Neurosci. 2005, 25:299-307.
30. Cordle A., Koenigsknecht-Talboo J., Wilkinson B., Limpert A., Landreth G. Mechanisms of statin-mediated inhibition of small G-protein function. J. Biol. Chem. 2005, 280:34202-34209.
31. Crestini A., Napolitano M., Piscopo P., Confaloni A., Bravo E. Changes in cholesterol metabolism are associated with PS1 and PS2 gene regulation in SK-N-BE. J. Mol. Neurosci. 2006, 30:311-322.
32. Crisby M., Carlson L.A., Winblad B. Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis. Assoc. Disord. 2002, 16:131-136.
33. 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. 2004, 101:2070-2075.
34. De Strooper B. Aph-1, Pen-2, and nicastrin with presenilin generate an active β-secretase complex. Neuron 2003, 38:9-12.
35. DeMattos R.B., Bales K.R., Cummins D.J., Dodart J.C., Paul S.M., Holtzman D.M. Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. 2001, 98:8850-8855.
36. Désiré L., Bourdin J., Loiseau N., Peillon H., Picard V., De Oliveira C., Bachelot F., Leblond B., Taverne T., Beausoleil E., Lacombe S., Drouin D., Schweighoffer F. RAC1 inhibition targets amyloid precursor protein processing by γ-secretase and decreases Aβ production in vitro and in vivo. J. Biol. Chem. 2005, 280:37516-37525.
37. Distl R., Meske V., T.G.O. Tangle-bearing neurons contain more free cholesterol than adjacent tangle-free neurons. Acta Neuropathol. 2001, 101:547-554.
38. Dominguez J.M., Muschamp J.W., Schmich J.M., Hull E.M. Nitric oxide mediates glutamate-evoked dopamine release in the medial preoptic area. Neuroscience 2004, 125:203-210.
39. Dugan J.M., deWit C., McCologues L., Maltese W.A. The Ras-related GTP-binding, Rab1B, regulates early steps in esocytic transport and processing of β-amyloid precursor protein. J. Biol. Chem. 1995, 270:10982-10989.
40. Ehehalt R., Keller P., Haass C., Thiele C., Simons K. Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J. Cell Biol. 2003, 160:113-123.
41. Ehrenstein M.R., Jury E.C., Mauri C. Statins for atherosclerosis-as good as it gets?. N. Engl. J. Med. 2005, 252:73-75.
42. Endo A., Kuroda M., Tanzawa K. Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett. 1976, 72:323-326.
43. Endres M. Statins and stroke. J. Cereb. Blood Flow Metab. 2005, 25:1093-1110.
44. Famer D., Crisby M. Rosuvastatin reduces caspase-3 activity and up-regulates α-secretase in human neuroblastoma SH-SY5Y cells exposed to Aβ. Neurosci. Lett. 2004, 271:209-214.
45. Fan Q.-W., Yu W., Senda T., Yanagisawa K., Michikawa M. Cholesterol-dependent modulation of tau phosphorylation in cultured neurons. J. Neurochem. 2001, 76:391-400.
46. Fan Q.-W., Yu W., Gong J.-S., Zou K., Sawamura N., Senda T., Yanagisawa K., Michikawa M. Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons. J. Neurochem. 2002, 80:178-190.
47. Farhangrazi Z.S., Ying H., Bu G., Dugan L.L., Fagan A.M., Choi D.W., Holtzman D.M. High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture. NeuroReport 1997, 8:1127-1130.
48. Farzan M., Schnitzler C.E., Vasilieva N., Leung D., Choe H. BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein. Proc. Natl. Acad. Sci. 2000, 97:9712-9717.
49. Fassbender K., Simons M., Bergmann C., Stroick M., Lütjohann D.P., Kelleri H.R., Kühl S., Bertsch T., Bergmann K.v., Hennerici M., Beyreuther K., Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease b-amyloid peptides Ab42 and Ab40 in vitro and in vivo. Proc. Natl. Acad. Sci. 2001, 98:5856-5861.
50. Ferreiro E., Oliveira C.R., Pereira C.M.F. The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol. Dis. 2008, 30:331-342.
51. Fischer H.-G., Reichmann G. Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J. Immunol. 2001, 166:2717-2726.
52. Fonseca, A.C., Proena, T., Resende, R., Oliveira, C.R., Pereira, C.M.F., 2009. Neuroprotective effects of statins in an in vitro model of Alzheimer's disease. J. Alzheimer's Dis. 17, 503-517.
53. Franke C., Nöldner M., Abdel-Kader R., Johnson-Anuna L.N., Wood W.G., Müller W.E., Eckert G.P. Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment. Neurobiol. Dis. 2007, 25:438-445.
54. Frears E.R., Stephens D.J., Walters C.E., Davies H., Austen B.M. The role of cholesterol in the biosynthesis of β-amyloid. NeuroReport 1999, 10:1699-1705.
55. García-Román N., Álvarez A.M., Toro M.J., Montes A., Lorenzo M.J. Lovastatin induces apoptosis of spontaneously immortalized rat brain neuroblasts: involvement of nonsterol isoprenoid biosynthesis inhibition. Mol. Cell. Neurosci. 2001, 17:329-341.
56. Gellermann G.P., Ullrich K., Tannert A., Unger C., Habicht G., Sauter S.R.N., Hortschansky P., Horn U., Möllmann U., Decker M., Lehmann J., Fändrich M. Alzheimer-like plaque formation by human macrophages Is reduced by fibrillation inhibitors and lovastatin. J. Mol. Biol. 2006, 360:251-257.
57. Gong J.-S., Sawamura N., Zou K., Sakai J., Yanagisawa K., Michikawa M. Amyloid β-protein affects cholesterol metabolism in cultured neurons: implications for pivotal role of cholesterol in the amyloid cascade. J. Neurosci. Res. 2002, 70:438-446.
58. Grace E.A., Rabiner C.A., Busciglio J. Characterization of neuronal dystrophy induced by fibrillar amyloid β: implications for Alzheimer's disease. Neuroscience 2002, 114:265-273.
59. Graves A.B., Rajaram L., Bowen J.D., McCormick W.C., McCurry S.M., Larson E.B. Cognitive decline and Japanese culture in a cohort of older Japanese Americans in King County, WA: the Kame Project. J. Gerontol., B Psychol. Sci. Soc. Sci. 1999, 54:S154-S161.
60. Grimm M.O., Grimm H.S., Pätzold A.J., Zinser E.G., Halonen R., Duering M., Tschäpe J.A., De Strooper B., Müller U., Shen J., Hartmann T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat. Cell Biol. 2005, 7:1118-1123.
61. Grimm M.O., Tschäpe J.A., Grimm H.S., Zinser E.G., Hartmann T. Altered membrane fluidity and lipid raft composition in presenilin-deficient cells. Acta Neurol. Scand. Suppl. 2006, 185:27-32.
62. Gustafson D., Rothenberg E., Blennow K., Steen B., Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch. Intern. Med. 2003, 163:1524-1528.
63. Hartmann T., Bieger S.C., Brühl B., Tienari P.J., Ida N., Allsop D., Roberts G.W., Masters C.L., Dotti C.G., Unsicker K., Beyreuther K. Distinct sites of intracellular production for Alzheimer's disease Abeta40/42 amyloid peptides. Nat. Med. 1997, 3:1016-1020.
64. Hayashi H., Kimura N., Yamaguchi H., Hasegawa K., Yokoseki T., Shibata M., Yamamoto N., Michikawa M., Yoshikawa Y., Terao K., Matsuzaki K., Lemere C.A., Selkoe D.J., Naiki H., Yanagisawa K. A seed for Alzheimer amyloid in the brain. J. Neurosci. 2004, 24:4894-4902.
65. Helzner E.P., Luchsinger J.A., Scarmeas N., Cosentino S., Brickman A.M., Glymour M.M., Stern Y. Contribution of vascular risk factors to the progression in Alzheimer disease. Arch. Neurol. 2009, 66:343-348.
66. Hendrie H.C., Ogunniyi A., Hall K.S., Baiyewu O., Unverzagt F.W., Gureje O., Gao S., Evans R.M., Ogunseyinde A.O., Adeyinka A.O., Musick B., Hui S.L. Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana. JAMA 2001, 285:739-747.
67. Herz J., Beffert U. Apolipoprotein E receptors: linking brain development and Alzheimer's disease. Nat. Rev., Neurosci. 2000, 1:51-58.
68. Heverin M., Bogdanovic N., Lütjohann D., Bayer T., Pikuleva I., Bretillon L., Diczfalusy U., Winblad B., Björkhem 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.
69. Hofman A., Ott A., Breteler M.M.B., Bots M.L., Slooter A.J.C., Harskamp F.v., van Duijn C.N., Van Broeckhoven C., Grobbee D.E. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 1997, 349:151-154.
70. (1-42), and total β-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Arch. Neurol. 2004, 61:333-337.
71. Höglund K., Syversen S., Lewczuk P., Wallin A., Wiltfang J., Blennow K. Statin treatment and a disease-specific pattern of β-amyloid peptides in Alzheimer's disease. Exp. Brain Res. 2005, 164:205-214.
72. Honig L.S., Tang M.-X., Albert S., Costa R., Luchsinger J., Manly J., Stern Y., Mayeux R. Stroke and the risk of Alzheimer disease. Arch. Neurol. 2003, 60:1707-1712.
73. Howland D.S., Trusko S.P., Savage M.J., Reaume A.G., Lang D.M., Hirsch J.D., Maeda N., Siman R., Greenberg B.D., Scott R.W., Flood D.G. Modulation of secreted β-amyloid precursor protein and amyloid β-peptide in brain by cholesterol. J. Biol. Chem. 1998, 273:16576-16582.
74. Hutter-Paier B., Huttunen H.J., Puglielli L., Eckman C.B., Kim D.Y., Hofmeister A., Moir R.D., Domnitz S.B., Frosch M.P., Windisch M., Kovacs D.M. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron 2004, 44:227-238.
75. Igbavboa U., Avdulov N.A., Schroeder F., Wood W.G. Increasing age alters transbilayer fluidity and cholesterol asymmetry in synaptic plasma membranes of mice. J. Neurochem. 1996, 66:1717-1725.
76. Igbavboa U., Pidcock J.M., Johnson L.N.A., Malo T.M., Studniski A.E., Yu S., Sun G.Y., Wood W.G. Cholesterol distribution in the Golgi complex of DITNC1 astrocytes is differentially altered by fresh and aged amyloid β-peptide-(1-42). J. Biol. Chem. 2003, 278:17150-17157.
77. Istvan E.S. Structural mechanism for statin inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Am. Heart J. 2002, 144:S27-S32.
78. Istvan E. Statin inhibition of HMG-CoA reductase: a 3-dimensional view. Atheroscler. Suppl. 2003, 4:3-8.
79. Jantzen F., Könemann S., Wolff B., Barth S., Staudt A., Kroemer H.-K., Dahm J.B., Felix S.B., Landsberger M. Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells. J. Physiol. Pharmacol. 2007, 58:503-514.
80. Jiang J.L., Wang S., Li N.S., Zhang X.H., Deng H.W., Li Y.J. The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is mediated by MAPK pathways in endothelial cells. Biochem. Cell. Biol. 2007, 85:66-77.
81. Jick H., Zornberg G.L., Jick S.S., Seshadri S., Drachman D.A. Statins and the risk of dementia. Lancet 2000, 356:1627-1631.
82. Jin L.-W., Maezawa I., Vincent I., Bird T. Intracellular accumulation of amyloidogenic fragments of amyloid-β precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities. Am. J. Pathol. 2004, 164:975-985.
83. Johnson-Anuna L.N., Eckert G.P., Keller J.H., Igbavboa U., Franke C., Fechner T., Schubert-Zsilavecz M., Karas M., Müller W.E., Wood W.G. Chronic administration of statins alters multiple gene expression patterns in mouse cerebral cortex. J. Pharmacol. Exp. Ther. 2005, 312:786-793.
84. Johnson-Anuna L.N., Eckert G.P., Franke C., Igbavboa U., Müller W.E., Wood W.G. Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. J. Neurochem. 2007, 101:77-86.
85. Jones P.H., Davidson M.H., Stein E.A., Bays H.E., McKenney J.M., Miller E., Cain V.A., Blasetto J.W., Group f.t.S.S. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am. J. Cardiol. 2003, 92:152-160.
86. Kaether C., Haass C. A lipid boundary separates APP and secretases and limits amyloid β-peptide generation. J. Cell Biol. 2004, 167:809-812.
87. Kakio A., Nishimoto S.-i., Yanagisawa K., Kozutsumi Y., Matsuzaki K. Interactions of amyloid β-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer Amyloid. Biochemistry 2002, 41:7385-7390.
88. 26]β-amyloid 1-14 to toxic and proteinase-resistant fragments. Neuroscience 2001, 104:1003-1011.
89. Karten B., E.Vance D., B.Campenot R., E.Vance J. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J. Neurochem. 2002, 83:1154-1163.
90. Kawas C., Gray S., Brookmeyer R., Fozard J., Zonderman A. Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 2000, 54:2072-2077.
91. Kiener P.A., Davis P.M., Murray J.L., Youssef S., Rankin B.M., Kowala M. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int. Immunopharmacol. 2001, 1:105-118.
92. Kirsh C., Eckert G.P., Mueller W.E. Statins effects on cholesterol micro-domains in plasma membranes. Biochem. Pharmacol. 2003, 65:843-856.
93. Kivipelto M., Helkala E., Laakso M.P., Hänninen T., Hallikainen M., Alhainen K., Soininen H., Tuomilehto J., Nissien A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001, 322:1447-1451.
94. Kivipelto M., Helkala E.L., Laakso M.P., Hänninen T., Hallikainen M., Alhainen K., Iivonen S., Mannermaa A., Tuomilehto J., Nissinen A., Soininen H. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann. Int. Med. 2002, 137:149-155.
95. Koike H., Tomioka S., Sorimachi H., Saido T.C., Maruyama K., Okuyama A., Fujisawa-Sehara A., Ohno S., Suzuki K., Ishiura S. Membrane-anchored metalloprotease MDC9 has an a-secretase activity responsible for processing the amyloid precursor protein. Biochem. J. 1999, 343:371-375.
96. Kojro E., Gimpl G., Lammich S., März W., Fahrenholz F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10. Proc. Natl. Acad. Sci. 2001, 98:5815-5820.
97. Koldamova R.P., Lefterov I.M., Ikonomovic M.D., Skoko J., Lefterov P.I., Isanski B.A., DeKosky S.T., Lazo J.S. 22R-Hydroxycholesterol and 9-cis-retinoic acid Induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid β secretion. J. Biol. Chem. 2003, 278:13244-13256.
98. Koudinov A.R., Koudinova N.V. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. 2001, 15:1858-1860.
99. Koudinov A.R., Koudinova N.V. Cholesterol homeostasis failure as a unifying cause of synaptic degeneration. J. Neurol. Sci. 2005, 229-230:233-240.
100. Kuo Y.-M., Emmerling M.R., Bisgaier C.L., Essenburg A.D., Lampert H.C., Drumm D., Roher A.E. Elevated low-density lipoprotein in Alzheimer's disease correlates with brain Aβ 1-42 levels. Biochem. Biophys. Res. Commun. 1998, 252:711-715.
101. Kureishi Y., Luo Z., Shiojima I., Bialik A., Fulton D., Lefer D.J., Sessa W.C., Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat. Med. 2000, 6:1004-1010.
102. Lacko A.G., Hayes J.D., McConathy W.J., Lacko I., Redheendran R. Lecithin: cholesterol acyltransferase in Down's syndrome. Clin. Chim. Acta 1983, 132:133-141.
103. Leissring M.A., Murphy M.P., Mead T.R., Akbari Y., Sugarman M.C., Jannatipour M., Anliker B., Müller U., Saftig P., Strooper B.D., Wolfe M.S., Golde T.E., LaFerla F.M. A physiologic signaling role for the γ-secretase-derived intracellular fragment of APP. Proc. Natl. Acad. Sci. 2002, 99:4697-4702.
104. Li X., Zuo P. Effects of Abeta25-35 on neurogenesis in the adult mouse subventricular zone and dentate gyrus. Neurol. Res. 2005, 27:218-222.
105. Li X., Liu L., Tupper J.C., Bannerman D.D., Winn R.K., Sebti S.M., Hamilton A.D., Harlan J.M. Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J. Biol. Chem. 2002, 277:15309-15316.
106. Li G., Higdon R., Kukull W.A., Peskind E., Van Valen M.K., Tsuang D., van Belle G., McCormick W.C., Bowen J.D., Teri L., Schellenberg G.D., Larson E.B. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neuron 2004, 63:1624-1628.
107. Li L., Cao D., Kim H., Lester R., Fukuchi K.-i. Simvastatin enhances learning and memory independent of amyloid load in mice. Ann. Neurol. 2006, 60:729-739.
108. Liao J.K. Isoprenoids as mediators of the biological effects of statins. J. Clin. Invest. 2002, 110:285-288.
109. Liu Y., Peterson D.A., Schubert D. Amyloid β peptide alters intracellular vesicle trafficking and cholesterol homeostasis. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:13266-13271.
110. Liu R., McAllister C., Lyubchenko Y., Sierks M.R. Residues 17-20 and 30-35 of beta-amyloid play critical roles in aggregation. J. Neurosci. Res. 2004, 75:162-171.
111. Locatelli S., Lutjohann D., Schmidt H.H., 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.
112. Lütjohann D., von Bergmann K. 24S-hydroxycholesterol: a marker of brain cholesterol metabolism. Pharmacopsychiatry 2003, 36:S102-S106.
113. Lütjohann D., Papassotiropoulos A., Björkhem I., Locatelli S., Bagli M., Oehring R.D., Schlegel U., Jessen F., Rao M.L., Bergmann K.v., Heun R. Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J. Lipid Res. 2000, 41:195-198.
114. Mackay D.J.G., Hall A. Rho GTPases. J. Biol. Chem. 1998, 273:20685-20688.
115. Malaplate-Armand C., Florent-Béchard S., Youssef I., Koziel V., Sponne I., Kriem B., Leininger-Muller B., Olivier J.-L., Oster T., Pillot T. Soluble oligomers of amyloid-B peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol. Dis. 2006, 23:178-189.
116. Marx J. Alzheimer's disease. Bad for the heart, bad for the mind?. Science 2001, 294:508-509.
117. März P., Otten U., Miserez A. Statins induce differentiation and cell death in neurons and astroglia. GLIA 2007, 55:1-12.
118. Mauch D.H., Nagler K., Schumacher S., Goritz C., Muller E.C., Otto A., Pfrieger F.W. CNS synaptogenesis promoted by glia-derived cholesterol. Science 2001, 294:1354-1357.
119. McConlogue L., Castellano F., deWit C., Schenk D., Maltese W.A. Differential effects of a Rab6 mutant on secretory versus amyloidogenic processing of Alzheimer's beta-amyloid precursor protein. J. Biol. Chem. 1996, 271:1343-1348.
120. Merla R., Ye Y., Lin Y., Manickavasagam S., Huang M.-H., Perez-Polo R.J., Uretsky B.F., Birnbaum Y. The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation. Am. J. Physiol., Heart Circ. Physiol. 2007, 293:H1918-H1928.
121. 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 geranylgeranyl pyrophosphate formation: implications for Alzheimer's disease. Eur. J. Neurosci. 2003, 17:93-102.
122. Michikawa M., Gong J.-S., Fan Q.-W., Sawamura N., Yanagisawa K. A novel action of Alzheimer's amyloid β-protein (Aβ): oligomeric Aβ promotes lipid release. J. Neurosci. 2001, 21:7226-7235.
123. Mielke M.M., Zandi P.P., Sjögren M., Gustafson D., Ostling S., Steen B., Skoog I. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology 2005, 64:1689-1695.
124. Mizuno T., Nakata M., Naiki H., Michikawa M., Wangi R., Haass C., Yanagisawa K. Cholesterol-dependent generation of a seeding amyloid beta-protein in cell culture. J. Biol. Chem. 1999, 274:15110-15114.
125. Montaner S., Perona R., Saniger L., Lacal J.C. Multiple signalling pathways lead to the activation of the nuclear factor kappaB by the Rho family of GTPases. J. Biol. Chem. 1998, 273:12779-12785.
126. Mozayan M., Lee T.J.F. Statins prevent cholinesterase inhibitor blockade of sympathetic α7-nAChR-mediated currents in rat superior cervical ganglion neurons. Am. J. Physiol., Heart Circ. Physiol. 2007, 293:H1737-H1744.
127. Mulhaupt F., Matter C.M., Kwak B.R., Pelli G., Veillard N.R., Burger F., Graber P., Lüscher T.F., Mach F. Statins (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells. Cardiovasc. Res. 2003, 59:755-766.
128. Nagy Z. The last neuronal division: a unifying hypothesis for the pathogenesis of Alzheimer's disease. J. Cell Mol. Med. 2005, 9:531-541.
129. Nelson T.J., Alkon D.L. Oxidation of cholesterol by amyloid precursor protein and β-amyloid peptide. J. Biol. Chem. 2005, 280:7377-7387.
130. Nixon R.A. Niemann-Pick type C disease and Alzheimer's disease: the APP-endosome connection fattens up. Am. J. Pathol. 2004, 64:757-761.
131. Olesen O.F., Dagø L. High density lipoprotein inhibits assembly of amyloid beta-peptides into fibrils. Biochem. Biophys. Res. Commun. 2000, 270:62-66.
132. Ong W.-Y., Kumar U., Switzer R.C., Sidhu A., Suresh G., Hu C.-Y., Patel S.C. Neurodegeneration in Niemann-Pick type C disease mice. Exp. Brain Res. 2001, 141:218-231.
133. Ostrowski S.M., Wilkinson B.L., Golde T.E., Landreth G. Statins reduce amyloid-β production through inhibition of protein isoprenylation. J. Biol. Chem. 2007, 282:26832-26844.
134. Pahan K., Sheikh F.G., Namboodiri A.M.S., Singh I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest. 1997, 100:2671-2679.
135. Panza F., D'Introno A., Colacicco A.M., Capurso C., Pichichero G., Capurso S.A., Capurso A., Solfrizzi V. Lipid metabolism in cognitive decline and dementia. Brain Res. Rev. 2006, 51:275-292.
136. Panza F., Capurso C., D'Introno A., Colacicco A.M., Candia D.D., Capurso A., Solfrizzi V. Total cholesterol levels and the risk of mild cognitive impairment and Alzheimer'disease. JAGS Lett. Ed. 2007, 55:133-135.
137. Papassotiropoulos A., Lutjohann D., Bagli M., Locatelli S., Jessen F., Buschfort R., Ptok U., Bjorkhem I., von Bergmann K., Heun R. 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia. J. Psychiatr. Res. 2002, 36:27-32.
138. Papassotiropoulos A., Streffer J.R., Tsolaki M., Schmid S., Thal D., Nicosia F., Iakovidou V., Maddalena A., Lütjohann D., Ghebremedhin E., Hegi T., Pasch T., Träxler M., Brühl 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.
139. Pappolla M.A., Bryant-Thomas T.K., Herbert D., Pacheco J., Fabra Garcia M., Manjon M., Girones X., Henry T.L., Matsubara E., Zambon D., Wolozin B., Sano M., Cruz-Sanchez F.F., Thal L.J., Petanceska S.S., Refolo L.M. Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 2003, 61:199-205.
140. Paris D., Townsend K.P., Humphrey J., Obregon D.F., Yokota K., Mullan M. Statins inhibit A beta-neurotoxicity in vitro and A beta-induced vasoconstriction and inflammation in rat aortae. Atherosclerosis 2002, 161:293-299.
141. Park I.-H., Hwang E.M., Hong H.S., Boo J.H., Oh S.S., Lee J., Jung M.W., Bang O.Y., Kima S.U., Mook-Jung I. Lovastatin enhances Aβ production and senile plaque deposition in female Tg2576 mice. Neurobiol. Aging 2003, 24:637-643.
142. Parsons R.B., Price G.C., Farrant J.K., Subramaniam D., Adeagbo-Sheikh J., Austen B.M. Statins inhibit the dimerization of beta-secretase via both isoprenoid- and cholesterol-mediated mechanisms. Biochem. J. 2006, 399:205-214.
143. Pedrini S., Carter T.L., Prendergast G., Petanceska S., Ehrlich M.E., Gandy S. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLOS Med. 2005, 2:69-78.
144. Peila R., Rodriguez B.L., Launer L.J. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia aging study. Diabetes 2002, 51:1256-1262.
145. Petanceska S.S., DeRosa S., Olm V., Diaz N., Sharma A., Thomas-Bryant T., Duff K., Pappolla M.A., Refolo L.M. Statin therapy for Alzheimer's disease: will it work?. J. Mol. Neurosci. 2002, 19:155-161.
146. Pfrieger F.W. Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes?. BioEssays 2003, 25:72-78.
147. Poirier J. Apolipoprotein E and Alzheimer's disease. A role in amyloid catabolism. Ann. N.Y. Acad. Sci. 2000, 924:81-90.
148. Pooler A.M., Xi S.C., Wurtman R.J. The 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin enhances neurite outgrowth in hippocampal neurons. J. Neurochem. 2006, 97:716-723.
149. Postina R., Schroeder A., Dewachter I., Bohl J., Schmitt U., Kojro E., Prinzen C., Endres K., Hiemke C., Blessing M., Flamez P., Dequenne A., Godaux E., Leuven F.v., Fahrenholz F. A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J. Clin. Invest. 2004, 113:1456-1464.
150. 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-coenyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat. Cell Biol. 2001, 3:905-912.
151. Puglielli L., Tanzi R.E., Kovacs D.M. Alzheimer's disease: the cholesterol connection. Nat. Neurosci. 2003, 6:345-351.
152. 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.
153. Qiu C., Winblad B., Viitanen M., Fratiglioni L. Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: a community based, longitudinal study. Stroke 2003, 34:594-599.
154. Refolo L.M., Pappolla M.A., Malester B., LaFrancois J., Bryant-Thomas T., Wang R., Tint G.S., Sambamurti K., Duff K.E. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol. Dis. 2000, 7:321-331.
155. 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.
156. Repetto E., Russo C., Venezia V., Nizzari M., Nitsch R.M., Schettini G. BACE1 overexpression regulates amyloid precursor protein cleavage and interaction with the ShcA adapter. Ann. N.Y. Acad. Sci. 2004, 1030:330-338.
157. 2+ homeostasis. Brain Res. 2007, 1143:11-21.
158. Resende R., Ferreiro E., Pereira C., Oliveira C.R. Neurotoxic effect of oligomeric and fibrillar species of Aβ1-42 peptide: involvement of endoplasmic reticulum calcium release in oligomers-induced cell death. Neuroscience 2008, 155:725-737.
159. Romas S., Tang M., Berglund L., Mayeux R. APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 1999, 53:517-521.
160. Runz H., Rietdorf J., Tomic I., Bernard M.d., 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.
161. Rutishauser J. The role of statins in clinical medicine-LDL-cholesterol lowering and beyond. Swiss Med. Wkly. 2006, 136:41-49.
162. Sabbagh M., Sahiri H.R., Ceimo J., Cooper K., Gaul W., Connor D., Sparks D.L. Is there a characteristic lipid profile in Alzheimer's disease. J. Alzheimer's Dis. 2004, 6:585-589.
163. Sala S.G., Muñoz Ú., Bartolomé F., Bermejo F., Martín-Requero Á. HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol lowering effects. J. Pharmacol. Exp. Ther. 2008, 324:352-359.
164. Salins P., Shawesh S., He Y., Dibrov A., Kashour T., Arthur G., Amara F. Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling. Neurosci. Lett. 2007, 412:211-216.
165. Schneider A., Schulz-Schaeffer W., Hartmann T., Schulz J.B., Simons M. Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons. Neurobiol. Dis. 2006, 23:573-577.
166. Schönknecht P., Lütjohann D., Pantel J., Bardenheuer H., Hartmann T., von Bergmann K., Beyreuther K., Schröder J. Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer's disease compared to healthy controls. Neurosci. Lett. 2002, 324:83-85.
167. Schroeder F., Gallegos A.M., Atshaves B.P., Storey S.M., McIntosh A.L., Petrescu A.D., Huang H., Starodub O., Chao H., Yang H., Frolov A., Kier A.B. Recent advances in membrane microdomains: rafts, caveolae, and intracellular cholesterol trafficking. Exp. Biol. Med. 2001, 226:873-890.
168. Schulz J.G., Bösel J., Stoeckel M., Megow D., Dirnagl U., Endres M. HMG-CoA reductase inhibition causes neurite loss by interfering with geranylgeranylpyrophosphate synthesis. J. Neurochem. 2004, 89:24-32.
169. Shepherd J., Blauw G.J., Murphy M.B., Bollen E.L.E.M., Buckley B.M., Cobbe S.M., Ford I., Gaw A., Hyland M., Jukema J.W., Kamper A.M., Macfarlane P.W., Meinders A.E., Norrie J., Packard C.J., Perry I.J., Stott D.J., Sweeney B.J., Twomey C., Westendorp R.G.J., group P.s. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002, 360:1623-1630.
170. Shie F.S., Jin L.W., Cook D.G., Leverenz J.B., LeBoeuf R.C. Diet-induced hypercholesterolemia enhances brain Aβ accumulation in transgenic mice. NeuroReport 2002, 13:455-459.
171. Shishehbor M.H., Brennan M.-L., Aviles R.J., Fu X., Penn M.S., Sprecher D.L., Hazen S.L. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 2003, 108:426-431.
172. Si M.L., Long C., Yang D.I., Chen M.F., Lee T.J. Statins prevent beta-amyloid inhibition of sympathetic alpha7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries. J. Cereb. Blood Flow Metab. 2005, 25:1573-1585.
173. Simons M., Keller P., De Strooper B., Beyreuther K., Dotti C.G., Simons K. Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:6460-6464.
174. Simons M., Keller P., Dichgans J., Schulz J. Cholesterol and Alzheimer's disease: is there a link?. Neurology 2001, 57.
175. Sjögren M., Gustafsson K., Syversen S., Olsson A., Edman Å., Davidsson P., Wallin A., Blennow K. Treatment with simvastatin in patients with Alzheimer's disease lowers both α- and β-cleaved APP. Dement. Geriatr. Cogn. Disord. 2003, 16:25-30.
176. Skovronsky D.M., Moore D.B., Milla M.E., Doms R.W., Lee V.M.-Y. Protein kinase C-dependent β-secretase competes with β-secretase for cleavage of amyloid-β precursor protein in the trans-golgi network. J. Biol. Chem. 2000, 275:2568-2575.
177. Solfrizzi V., Panza F., Colacicco A.M., D'Introno A., Capurso C., Torres F., Grigoletto F., Maggi S., Del Parigi A., Reiman E.M., Caselli R.J., Scafato E., Farchi G., Capurso A., Group I.L.S.o.A.W. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004, 63:1882-1891.
178. Sparks D.L., Hunsaker J.C.r., Scheff S.W., Kryscio R.J., Henson J.L., Markesbery W.R. Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease. Neurobiol. Aging 1990, 11:601-607.
179. Sparks D.L., Sabbagh M.N., Breitner J.C.S., Hunsaker J. Is cholesterol a culprit in Alzheimer's disease?. Int. Psychogeriatr. 2003, 15:153-159.
180. Sparks D.L., Sabbagh M.N., Connor D.J., Lopez J., Launer L.J., Browne P., Wassar D., Johnson-Traver S., Lochhead J., Ziolwolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease. Arch. Neurol. 2005, 62:753-757.
181. Sponne I., Fifre A., Kriem B., Koziel V., Bihain B., Oster T., Olivier J.-L., Pillot T. Membrane cholesterol interferes with neuronal apoptosis induced by soluble oligomers but not fibrils of amyloid-β peptide. FASEB J. 2004, 18:836-838.
182. Stephens D.J., Austen B.M. Metabolites of the β-amyloid precursor protein generated by β-secretase localise to the trans-Golgi network and late endosome in 293 cells. J. Neurosci. Res. 1996, 46:211-225.
183. Strittmatter W.J., Weisgraber K.H., Huang D.Y., Dong L.-M., Salvesen G.S., Pericak-Vance M., Schmechel D., Saunders A.M., Goldgaber D., Roses A.D. Binding of human apolipoprotein E to synthetic amyloid β peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 1993, 90:8098-8102.
184. Subasinghe S., Unabia S., Barrow C.J., Mok S.S., Aguilar M.-I., Small D.H. Cholesterol is necessary both for the toxic effect of Aβ peptides on vascular smooth muscle cells and for Aβ binding to vascular smooth muscle cell membranes. J. Neurochem. 2003, 84:471-479.
185. Sun Y.-X., Crisby M., Lindgren S., Janciauskiene S. Pravastatin inhibits pro-inflammatory effects of Alzheimer's peptide Aβ1-42 in glioma cell culture in vitro. Pharmacol. Res. 2003, 47:119-126.
186. Svennerholm L., Bostr6m K., Jungbjer B., Olsson L. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem. 1994, 63:1802-1811.
187. Tadiboyina V.T., Liu D.M., Miskie B.A., Wang J., Hegele R.A. Treatment of dyslipidemia with lovastatin and ezetimibe in an adolescent with cholesterol ester storage disease. Lipids Health Dis. 2005, 4:26-31.
188. Tanaka T., Tatsuno I., Uchida D., Moroo I., Morio H., Nakamura S., Noguchi Y., Yasuda T., Kitagawa M., Saito Y., Hirai A. Geranylgeranyl-pirophosphate, an isoprenoid of mevalonate cascade, is a critical compound for rat primary cultured cortical neurons to protect the cell death induced by 3-hydroxy-3-methylglutaryl-CoA reductase inhibition. J. Neurosci. 2000, 20:2852-2859.
189. Tomita T., Maruyana K., Saido T.C., Kume H., Shinozaki K., Tokuhiro S., Capell A., Walter J., Grünberg J., Haass C., Iwatsubo T., Obata K. The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:2025-2030.
190. Townsend K.P., Shytle D.R., Bai Y., San N., Zeng J., Freeman M., Mori T., Fernandez F., Morgan D., Sanberg P., Tan J. Lovastatin modulation of microglial activation via suppression of functional CD40 expression. J. Neurosci. Res. 2004, 78:167-176.
191. Urano Y., Hayashi I., Isoo N., Reid P.C., Shibasaki Y., Noguchi N., Tomita T., Iwatsubo T., Hamakubo T., Kodama T. Association of active γ-secretase complex with lipid rafts. J. Lipid Res. 2005, 46:904-912.
192. Urbich C., Dernbach E., Zeiher A.M., Dimmeler S. Double-edged role of statins in angiogenesis signaling. Circ. Res. 2002, 90:737-744.
193. Veillard N.R., Mach F. Statins: the new aspirin?. Cell. Mol. Life Sci. 2002, 59:1771-1786.
194. Vetrivel K.S., Cheng H., Lin W., Sakurai T., Li T., Nukina N., Wong P.C., Xu H., Thinakaran G. Association of γ-secretase with lipid raft in post-Golgi and endossome membrane. J. Biol. Chem. 2004, 279:44945-44954.
195. Wagner A.H., Gebauer M., Güldenzoph B., Hecker M. 3-Hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2002, 22:1784-1789.
196. Wahrle S., Das P., Nyborg A.C., McLendon C., Shoji M., Kawarabayashi T., Younkin L.H., Younkin S.G., Golde T.E. Cholesterol-dependent γ-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol. Dis. 2002, 9:11-23.
197. Wang Q., Ting W.L., Yang H., Wong P.T.-H. High doses of simvastatin upregulate dopamine D1 and D2 receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase. Br. J. Pharmacol. 2005, 144:933-939.
198. Weis M., Heeschen C., Glassford A.J., Cooke J.P. Statins have biphasic effects on angiogenesis. Circulation 2002, 105:739-745.
199. Weitz-Schmidt G., Welzenbach K., Brinkmann V., Kamata T., Kallen J., Bruns C., Cottens S., Takada Y., Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med. 2001, 7:687-692.
200. Wilson D.M., Binder L.I. Free fatty acids stimulate the polymerization of tau and amyloid β peptides: in vitro evidence for a common effector of pathogenesis in Alzheimer's disease. Am. J. Pathol. 1997, 150:2181-2195.
201. Wolf H., Hensel A., Arendt T., Kivipelto M., Winblad B., Gertz H.-J. Serum lipids and hippocampal volume: the link to Alzheimer's disease?. Ann. Neurol. 2004, 56:745-749.
202. Wolozin B. A fluid connection: cholesterol and Aβ. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:5371-5373.
203. Wolozin B. Cholesterol and Alzheimer's disease. Biochem. Soc. Trans. 2002, 30:525-529.
204. Wolozin B. Cholesterol, statins and dementia. Curr. Opin. Lipid. 2004, 15:667-672.
205. 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.
206. Wu Y., Sun F.F., Tong D.M., Taylor B.M. Changes in membrane properties during energy depletion-induced cell injury studied with fluorescence microscopy. Biophys. J. 1996, 71:91-100.
207. Xiao X.Q., Zhang H.Y., Tang X.C. Huperzine A attenuates amyloid β-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J. Neurosci. Res. 2002, 67:30-36.
208. Xiu J., Nordberg A., Shan K.-R., Yu W.-F., Olsson J.M., Nordman T., Mousavi M., Guan Z.Z. Lovastatin stimulates up-regulation of α7 nicotinic receptors in cultured neurons without cholesterol dependency, a mechanism involving production of the α-form of secreted amyloid precursor protein. J. Neurosci. Res. 2005, 82:531-541.
209. Yaffe K., Barret-Connor E., Lin F., Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch. Neurol. 2002, 59:378-384.
210. Yamazaki T., Chang T.-Y., Haass C., Ihara Y. Accumulation and aggregation of amyloid β-protein in late endosomes of Niemann-pick type C cells. J. Biol. Chem. 2001, 276:4454-4460.
211. Yao Z., Brow R., Teper G., Greeson J., Papadopoulos V. 22R-Hydroxycholesterol protects neuronal cells from beta-amyloid-induced cytotoxicity by binding to beta-amyloid peptide. Neurochemistry 2002, 83:1110-1119.
212. Yasojima K., McGeer E.G., McGeer P.L. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in Alzheimer and control brain. NeuroReport 2001, 12:2935-2938.
213. Youssef S., Stuve O., Patarroyo J.C., Ruiz P.J., Radosevich J.L., Hur E.M., Bravo M., Mitchell D.J., Sobel R.A., Steinman L., Zamvil S.S. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002, 420:78-84.
214. Zacco A., Togo J., Spence K., Ellis A., Lloyd D., Furlong S., Piser T. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect cortical neurons from excitotoxicity. J. Neurosci. 2003, 23:11104-11111.
215. Zandi P.P., Sparks L., Khachaturian A.S., Tschanz J., Norton M., Steinberg M., Welsh-Bohmer K.A., Breitner J.C.S., Investigators f.t.C.C.S. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch. Genet. Psychiatry 2005, 62:217-224.
216. Zekanowski C., Religa D., Graff C., Filipek S., Kuźnicki J. Genetic aspects of Alzheimer's disease. Acta Neurobiol. Exp. 2004, 64:19-31.
217. Zhou Y., Su Y., Li B., Liu F., Ryder J.W., Wu X., Gonzalez-DeWhitt P.A., Gelfanova V., Hale J.E., May P.C., Paul S.M., Ni B. Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Aβ42 by inhibiting Rho. Science 2003, 302:1215-1217.
218. Zhou B., Teramukai S., Fukushima M. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement. Geriatr. Cogn. Disord. 2007, 23:194-201.
219. Zhou Y., Suram A., Venugopal C., Prakasam A., Lin S., Su Y., Li B., Paul S.M., Sambamurti K. Geranylgeranyl pyrophosphate stimulates γ-secretase to increase the generation of Aβ and APP-CTFγ. FASEB J. 2008, 22:47-54.
220. Zigman W.B., Schupf N., Jenkins E.C., Urv T.K., Tycko B., Silverman W. Cholesterol level, statin use and Alzheimer's disease in adults with Down syndrome. Neurosci. Lett. 2007, 416:279-284.