Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy

Journal of Neuropathology and Experimental Neurology

Volumn 68, Issue 3, 2009, Pages 314-325

  Boimel, Moran ^a   Grigoriadis, Nikolaos ^b   Lourbopoulos, Athanassios ^b   Touloumi, Olga ^b   Rosenmann, David ^c   Abramsky, Oded ^a   Rosenmann, Hanna ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^c SHAARE ZEDEK MEDICAL CENTER   (Israel)

Author keywords

Alzheimer disease; Neurofibrillary tangles; Statins; Tau; Tauopathy

Indexed keywords

ATORVASTATIN; EZETIMIBE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LECTIN; SIMVASTATIN; TAU PROTEIN; AZETIDINE DERIVATIVE; HEPTANOIC ACID DERIVATIVE; PYRROLE DERIVATIVE;

AGED; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; BLOOD SAMPLING; BRAIN; CONTROLLED STUDY; DRUG EFFECT; HYPERCHOLESTEROLEMIA; MAZE TEST; MICROGLIA; MOUSE; NEUROFIBRILLARY TANGLE; NONHUMAN; PRIORITY JOURNAL; SPINAL CORD; TAUOPATHY; TRANSGENIC MOUSE; TREATMENT DURATION; ANIMAL; CAPILLARY PERMEABILITY; DIET; DISEASE MODEL; IMMUNOHISTOCHEMISTRY; PATHOLOGY;

ANIMALS; AZETIDINES; BRAIN; CAPILLARY PERMEABILITY; DIET; DISEASE MODELS, ANIMAL; HEPTANOIC ACIDS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; IMMUNOHISTOCHEMISTRY; MAZE LEARNING; MICE; MICE, TRANSGENIC; NEUROFIBRILLARY TANGLES; PYRROLES; SIMVASTATIN; SPINAL CORD; TAUOPATHIES;

EID: 65349152565     PISSN: 00223069     EISSN: None     Source Type: Journal    
DOI: 10.1097/NEN.0b013e31819ac3cb     Document Type: Article

References (52)

1. Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzymeA reductase inhibitors. Arch Neurol 2000;57:1439-43
2. Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet 2000;356:1627-31
3. Rockwood K, Kirkland S, Hogan DB, et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002;59:223-27
4. Hajjar I, Schumpert J, Hirth V, et al. The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol A Biol Sci Med Sci 2002;57:M414-18
5. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer's disease. Neuroepidemiology 2004;23:94-98
6. Dufouil C, Richard F, Fievet N, et al. APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: The Three-City Study. Neurology 2005;64:1531-38
7. Li G, Higdon R, Kukull WA, et al. Statin therapy and risk of dementia in the elderly: A community-based prospective cohort study. Neurology 2004;63:1624-28
8. Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008;70:1795-802
9. Rea TD, Breitner JC, Psaty BM, et al. Statin use and the risk of incident dementia: The Cardiovascular Health Study. Arch Neurol 2005;62:1047-51
10. Zandi PP, Sparks DL, Khachaturian AS, et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005;62:217-24
11. Sparks DL, Sabbagh MN, Connor DJ, et al. Atorvastatin for the treatment of mild to moderate Alzheimer disease: Preliminary results. Arch Neurol 2005;62:753-57
12. Youssef S, Stuve O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002;420:78-84
13. Endres M, Laufs U, Huang Z, et al. Stroke protection by 3-hydroxy- 3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 1998;95: 8880-85
14. Wolozin B, Wang SW, Li NC, et al. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med 2007;5:20
15. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005;45:89-118
16. Zipp F, Waiczies S, Aktas O, et al. Impact of HMG-CoA reductase inhibition on brain pathology. Trends Pharmacol Sci 2007;28:342-49
17. Chauhan NB, Siegel GJ, Feinstein DL. Effects of lovastatin and pravastatin on amyloid processing and inflammatory response in TgCRND8 brain. Neurochem Res 2004;29:1897-911
18. Fassbender K, Simons M, Bergmann C, et al. 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;98:5856-61
19. Park IH, Hwang EM, Hong HS, et al. Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol Aging 2003;24:637-43
20. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 1991;82:239-59
21. Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992;42:631-39
22. Oddo S, Caccamo A, Green KN, et al. Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease. Proc Natl Acad Sci U S A 2005;102:3046-51
23. Rosenmann H, Grigoriadis N, Eldar-Levy H, et al. A novel transgenic mouse expressing double mutant tau driven by its natural promoter exhibits tauopathy characteristics. Exp Neurol 2008;212:71-84
24. Li Y, Liu L, Barger SW, Griffin WS. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J Neurosci 2003;23:1605-11
25. Schneider A, Araujo GW, Trajkovic K, et al. Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis. J Biol Chem 2004;279:55833-39
26. Kitazawa M, Oddo S, Yamasaki TR, et al. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J Neurosci 2005;25:8843-53
27. Rosenmann H, Grigoriadis N, Karussis D, et al. Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch Neurol 2006;63:1459-67
28. Delsing DJ, Jukema JW, van de Wiel MA, et al. Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice. J Cardiovasc Pharmacol 2003;42:63-70
29. Davis HR Jr, Compton DS, Hoos L, Tetzloff G. Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. Arterioscler Thromb Vasc Biol 2001;21: 2032-38
30. Allain CC, Poon LS, Chan CS, et al. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-75
31. Gallyas F, Farkas O, Mazlo M. Gel-to-gel phase transition may occur in mammalian cells: Mechanism of formation of Bdark[ (compacted) neurons. Biol Cell 2004;96:313-24
32. Zsombok A, Toth Z, Gallyas F. Basophilia, acidophilia and argyrophilia of Bdark[ (compacted) neurons during their formation, recovery or death in an otherwise undamaged environment. J Neurosci Methods 2005;142: 145-52
33. 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;28:979-86
34. Saheki A, Terasaki T, Tamai I, Tsuji A. In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 1994;11:305-11
35. van Heek M, Austin TM, Farley C, et al. Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters. Diabetes 2001;50:1330-35
36. Ishizawa K, Dickson DW. Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration. J Neuropathol Exp Neurol 2001;60:647-57
37. Sato R, Takano T. Regulation of intracellular cholesterol metabolism. Cell Struct Funct 1995;20:421-27
38. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 1997;75:165-73
39. Kitazawa M, Yamasaki TR, LaFerla FM. Microglia as a potential bridge between the amyloid beta-peptide and tau. Ann N Y Acad Sci 2004; 1035:85-103
40. Townsend KP, Shytle DR, Bai Y, et al. Lovastatin modulation of microglial activation via suppression of functional CD40 expression. J Neurosci Res 2004;78:167-76
41. Lindberg C, Crisby M, Winblad B, Schultzberg M. Effects of statins on microglia. J Neurosci Res 2005;82:10-19
42. Cordle A, Landreth G. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J Neurosci 2005;25:299-307
43. Clarke RM, O'Connell F, Lyons A, Lynch MA. The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-beta1-42 in the rat hippocampus in vivo. Neuropharmacology 2007;52:136-45
44. Bi X, Baudry M, Liu J, et al. Inhibition of geranylgeranylation mediates the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors on microglia. J Biol Chem 2004;279:48238-45
45. Sparks DL, Connor DJ, Browne PJ, et al. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier. J Nutr Health Aging 2002;6:324-31
46. Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A 1997;94:4080-85
47. Mezey E, Chandross KJ, Harta G, et al. Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000;290:1779-82
48. Wardle J, Rogers P, Judd P, et al. Randomized trial of the effects of cholesterol-lowering dietary treatment on psychological function. Am J Med 2000;108:547-53
49. Parvathy S, Ehrlich M, Pedrini S, et al. Atorvastatin-induced activation of Alzheimer's alpha secretase is resistant to standard inhibitors of protein phosphorylation-regulated ectodomain shedding. J Neurochem 2004;90:1005-10
50. Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 2001;414:212-26
51. Li L, Cao D, Kim H, et al. Simvastatin enhances learning and memory independent of amyloid load in mice. Ann Neurol 2006;60:729-39
52. El Khoury J, Hickman SE, Thomas CA, et al. Scavenger receptormediatedadhesion of microglia to beta-amyloid fibrils. Nature 1996;382: 716-19