Statins- the future of Alzheimer’s disease treatment?
Keywords:
medicineAbstract
Emerging research indicates that the pathological basis of Alzheimer’s disease maybe inflammatory in origin, possibly mediated through the pro-inflammatory cytokine, interleukin-1beta. Statins are a class of drugs which reduce circulating lipid levels. There is also evidence that they may have anti-inflammatory properties. This review assesses new evidence that statin therapy may have a role in the treatment of Alzheimer’s disease.References
1.Jorm AF, Korten AE, Henderson AS . The prevalence of dementia: a quantitativeintegration of the literature. Acta Psych Scand 1978;76:465-9. 2.Wimo A, Winblad B, Aguero-Torres H, von Strauss E. The magnitude of dementiaoccurrence in the world. Alzheimer Disease and Associated Disorders2003;17: 63-7.
3.Schellenberg GD. Progress in Alzheimer’s disease genetics. Curr Opin Neurol1995;8:262-7.
4.Evans DA, Funkenstein HH, Albert MS et al. Prevalence of Alzheimer’s disease in acommunity population of older persons: higher than previously reported. JAMA1989;262:2551-6.
5.Hofman A, Ott A, Breteler MM et al. Atherosclerosis, apolipoprotein E, andprevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet1997;349:151-4.
6.Blessed G, Tomlinson BE, Roth M. The association between quantitative measures ofdementia and of senile changes in the cerebral gray matter of elderly subjects. Br J Psych1968;225:797-811.
7.Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI.Abnormal phosphorylation of the microtubule-associated protein Tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986;83:4913-7.
8. Monaco EA. Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer’s disease. Curr Alzheimer Res2004;1:33-8.
9. Neumann H.Control of glial immune function by neurons. Glia 2001;36:191-9.
10. Thornberry NA, Bull HG, Calaycay JR et al.A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes.Nature1992;356:768-74.
11. Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. NatRev2005;5:629-40.
12. GriffinWST, Stanley LC, Ling C et al.Brain interneukin 1 and S-100 immunoreactivity are elevated in Down Syndrome and Alzheimer Disease.ProcNatl Acad Sci USA1989;86:7611-5.
13. Hu S, Peterson PK, Chao CC.Cytokine-mediated neuronal apoptosis.NeurochemInt1997;30:427-31.
14. Minogue AM, Schmidt AW, Fogarty MP et al. Activation of the c-Jun N-terminal Kinase signaling cascade mediates the effect of amyloid-β on long term potentiation and cell death in hippocampus.JBiol Chem2003;278:27971-80.
15. Kim HD, Cao Y, Kong FKet al. Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF. Vaccine 2005;23:2977-86.
16. Mason RP, Walter MF, Day CA, Jacob RF.Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors contribute to distinct pharmacologicand pleiotropic actions. Am JCardiol2005;96:11F-23F.
17. Baigent C, Keech A, Kearney PMet al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet2005;366:1267-78.
18. Wierzbicki AS, Poston R, Ferro A. The lipid and non-lipid effects of statins. PharmacolTherap2003;9:95-112.
19. Kobashigawa JA, Katznelson S, Laks H et al. Effect of pravastatin on outcomes after cardiac transplantation. New Engl JMed1995;333:621-7.
20.Cutts JL, Scallen TJ, Watson J, Bankhurst AD. Reversal of lovastatin-mediated inhibition of natural killer cell cytotoxicity by interleukin 2. J CellPhysiol1990;145:244-52.
21. Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem1996;271:5289-92.
22.Takai Y, Sasaki T, Matozaki T.Small GTP-binding proteins. PhysiolRev2001;81:153-208.
23. Mackay DJ, Hall A.Rho GTPases. J BiolChem1998;273:20685-8.
24. Montaner S, Perona R, Saniger L, Lacal JC.Multiple Signaling Pathways Lead to the Activation of the Nuclear Factor κB by the Rho Family of GTPases.J BiolChem1998;278:12779-85.
25. Yang CC, Jick SS, Jick H.Statins and the risk of idiopathic venous thromboembolism. Br J Clin Pharmacol2002;53:101-5.
26. Sparks DL, Sabbagh MN, Connor DJ et al. Atorvastatin fro the treatment of mild to moderate Alzheimer disease. ArchNeurol2005;62:753-7.
27. 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.
28.Bodovitz S, Klein WL.Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein.J BiolChem1996;271:4436-40.
29. Cordle A, Landreth G.3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate β-amyloid-induced microglial inflammatory responses. JNeurosci2005;25:299-307.
30. Lindberg C, Crisby M, Winblad B, Schultzberg M.Effects of statins on microglia.J NeurosciRes2005;82:10-9.
31.Cordle A, Koenigsknecht-Talboo J, Wilkinson B, Limpert A, Landreth G.Mechanisms of statin-mediated inhibition of small G-protein function. J BiolChem2005;280:34202-9.
3.Schellenberg GD. Progress in Alzheimer’s disease genetics. Curr Opin Neurol1995;8:262-7.
4.Evans DA, Funkenstein HH, Albert MS et al. Prevalence of Alzheimer’s disease in acommunity population of older persons: higher than previously reported. JAMA1989;262:2551-6.
5.Hofman A, Ott A, Breteler MM et al. Atherosclerosis, apolipoprotein E, andprevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet1997;349:151-4.
6.Blessed G, Tomlinson BE, Roth M. The association between quantitative measures ofdementia and of senile changes in the cerebral gray matter of elderly subjects. Br J Psych1968;225:797-811.
7.Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI.Abnormal phosphorylation of the microtubule-associated protein Tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986;83:4913-7.
8. Monaco EA. Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer’s disease. Curr Alzheimer Res2004;1:33-8.
9. Neumann H.Control of glial immune function by neurons. Glia 2001;36:191-9.
10. Thornberry NA, Bull HG, Calaycay JR et al.A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes.Nature1992;356:768-74.
11. Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. NatRev2005;5:629-40.
12. GriffinWST, Stanley LC, Ling C et al.Brain interneukin 1 and S-100 immunoreactivity are elevated in Down Syndrome and Alzheimer Disease.ProcNatl Acad Sci USA1989;86:7611-5.
13. Hu S, Peterson PK, Chao CC.Cytokine-mediated neuronal apoptosis.NeurochemInt1997;30:427-31.
14. Minogue AM, Schmidt AW, Fogarty MP et al. Activation of the c-Jun N-terminal Kinase signaling cascade mediates the effect of amyloid-β on long term potentiation and cell death in hippocampus.JBiol Chem2003;278:27971-80.
15. Kim HD, Cao Y, Kong FKet al. Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF. Vaccine 2005;23:2977-86.
16. Mason RP, Walter MF, Day CA, Jacob RF.Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors contribute to distinct pharmacologicand pleiotropic actions. Am JCardiol2005;96:11F-23F.
17. Baigent C, Keech A, Kearney PMet al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet2005;366:1267-78.
18. Wierzbicki AS, Poston R, Ferro A. The lipid and non-lipid effects of statins. PharmacolTherap2003;9:95-112.
19. Kobashigawa JA, Katznelson S, Laks H et al. Effect of pravastatin on outcomes after cardiac transplantation. New Engl JMed1995;333:621-7.
20.Cutts JL, Scallen TJ, Watson J, Bankhurst AD. Reversal of lovastatin-mediated inhibition of natural killer cell cytotoxicity by interleukin 2. J CellPhysiol1990;145:244-52.
21. Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem1996;271:5289-92.
22.Takai Y, Sasaki T, Matozaki T.Small GTP-binding proteins. PhysiolRev2001;81:153-208.
23. Mackay DJ, Hall A.Rho GTPases. J BiolChem1998;273:20685-8.
24. Montaner S, Perona R, Saniger L, Lacal JC.Multiple Signaling Pathways Lead to the Activation of the Nuclear Factor κB by the Rho Family of GTPases.J BiolChem1998;278:12779-85.
25. Yang CC, Jick SS, Jick H.Statins and the risk of idiopathic venous thromboembolism. Br J Clin Pharmacol2002;53:101-5.
26. Sparks DL, Sabbagh MN, Connor DJ et al. Atorvastatin fro the treatment of mild to moderate Alzheimer disease. ArchNeurol2005;62:753-7.
27. 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.
28.Bodovitz S, Klein WL.Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein.J BiolChem1996;271:4436-40.
29. Cordle A, Landreth G.3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate β-amyloid-induced microglial inflammatory responses. JNeurosci2005;25:299-307.
30. Lindberg C, Crisby M, Winblad B, Schultzberg M.Effects of statins on microglia.J NeurosciRes2005;82:10-9.
31.Cordle A, Koenigsknecht-Talboo J, Wilkinson B, Limpert A, Landreth G.Mechanisms of statin-mediated inhibition of small G-protein function. J BiolChem2005;280:34202-9.
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Published
2006-01-01
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O’Connell, F. . (2006). Statins- the future of Alzheimer’s disease treatment?. Trinity Student Medical Journal , 7(1). Retrieved from https://ojs.tchpc.tcd.ie/index.php/tsmj/article/view/1858
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