Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 5, Issue 4 , Pages 348-360 , July 2009

Alzheimer's disease and infection: Do infectious agents contribute to progression of Alzheimer's disease?

  • Kie Honjo

      Affiliations

    • L.C. Campbell Cognitive Neurology Research Unit, Heart and Stroke Foundation Centre for Stroke Recovery, Section of Neurology, Department of Medicine, Sunnybrook Health Science Centre and University of Toronto, Toronto, Ontario, Canada
    • Kunin-Lunenfeld Applied Research Unit, Baycrest, Toronto, Ontario, Canada
    • ,
  • Robert van Reekum

      Affiliations

    • Kunin-Lunenfeld Applied Research Unit, Baycrest, Toronto, Ontario, Canada
    • ,
  • Nicolaas P.L.G. Verhoeff

      Affiliations

    • Kunin-Lunenfeld Applied Research Unit, Baycrest, Toronto, Ontario, Canada
    • Corresponding Author InformationCorresponding author. Tel.: +1-416-785-2500. ext. 2167; Fax: +1-416-785-4230.

References 

  1. Alzheimer's Disease International. Media quick facts: the global impact of dementia. London: Alzheimer's Disease International; 1997–2007. Updated December 15, 2005; cited July 25, 2007. Available from: http://www.alz.co.uk/media/dementia.html.
  2. Office of Science Policy Analysis. Economic studies program: disease-specific estimates of direct and indirect costs and NIH support. Fiscal year 2000 update. Bethesda, MD: National Institutes of Health. Updated June 2, 2000; cited July 25, 2007. Available from: http://ospp.od.nih.gov/ecostudies/COIreportweb.html.
  3. Roth M. The natural history of mental disorder in old age. J Ment Sci. 1955;101:281–301
  4. de la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke. 2002;33:1152–1162
  5. Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke. 2004;35(Suppl. 1):2620–2622
  6. Cleobury JF, Skinner GR, Thouless ME, Wildy P. Association between psychopathic disorder and serum antibody to herpes simplex virus (type 1). Br Med J [Clin Res]. 1971;1:438–439
  7. Lycke E, Norrby R, Roos BE. A serological study on mentally ill patients with particular reference to the prevalence of herpes virus infections. Br J Psychiatry. 1974;124:273–279
  8. Sequiera LW, Jennings LC, Carrasco LH, Lord MA, Curry A, Sutton RN. Detection of herpes-simplex viral genome in brain tissue. Lancet. 1979;2:609–612
  9. Middleton PJ, Petric M, Kozak M, Rewcastle NB, McLachlan DR. Herpes-simplex viral genome and senile and presenile dementias of Alzheimer and Pick. Lancet. 1980;1:1038
  10. Pogo BG, Casals J, Elizan TS. A study of viral genomes and antigens in brains of patients with Alzheimer's disease. Brain. 1987;110:907–915
  11. Pogo BG, Elizan TS. Search for viral DNA sequences in Alzheimer brain tissue. Lancet. 1985;1:978–979
  12. Renvoize EB, Awad IO, Hambling MH. A sero-epidemiological study of conventional infectious agents in Alzheimer's disease. Age Ageing. 1987;16:311–314
  13. Renvoize EB, Hambling MH. Cytomegalovirus infection and Alzheimer's disease. Age Ageing. 1984;13:205–209
  14. Jamieson GA, Maitland NJ, Wilcock GK, Craske J, Itzhaki RF. Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains. J Med Virol. 1991;33:224–227
  15. Jamieson GA, Maitland NJ, Wilcock GK, Yates CM, Itzhaki RF. Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type. J Pathol. 1992;167:365–368
  16. Miklossy J. Alzheimer's disease—a spirochetosis?. Neuroreport. 1993;4:841–848
  17. Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H. Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer's disease. Neuroreport. 1994;5:1201–1204
  18. Balin BJ, Gerard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, et al. Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Med Microbiol Immunol (Berl). 1998;187:23–42
  19. Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology. 2006;66:938–940
  20. Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, et al. Borrelia burgdorferi persists in the brain in chronic Lyme neuroborreliosis and may be associated with Alzheimer disease. J Alzheimers Dis. 2004;6:639–649
  21. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000;21:383–421
  22. Mamelak M. Alzheimer's disease, oxidative stress and gammahydroxybutyrate. Neurobiol Aging. 2007;28:1340–1360
  23. Stichel CC, Luebbert H. Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol Aging. 2007;28:1507–1521
  24. Lin WR, Jennings R, Smith TL, Wozniak MA, Itzhaki RF. Vaccination prevents latent HSV1 infection of mouse brain. Neurobiol Aging. 2001;22:699–703
  25. Wozniak MA, Shipley SJ, Combrinck M, Wilcock GK, Itzhaki RF. Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer's disease patients. J Med Virol. 2005;75:300–306
  26. Becker Y. HSV-1 brain infection by the olfactory nerve route and virus latency and reactivation may cause learning and behavioral deficiencies and violence in children and adults: a point of view. Virus Genes. 1995;10:217–226
  27. Boggian I, Buzzacaro E, Calistri A, Calvi P, Cavaggioni A, Mucignat-Caretta C, et al. Asymptomatic herpes simplex type 1 virus infection of the mouse brain. J Neurovirol. 2000;6:303–313
  28. Gordon L, McQuaid S, Cosby SL. Detection of herpes simplex virus (types 1 and 2) and human herpesvirus 6 DNA in human brain tissue by polymerase chain reaction. Clin Diagn Virol. 1996;6:33–40
  29. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. Lancet. 1997;349:241–244
  30. Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF. Herpesviruses in brain and Alzheimer's disease. J Pathol. 2002;197:395–402
  31. Beffert U, Bertrand P, Champagne D, Gauthier S, Poirier J. HSV-1 in brain and risk of Alzheimer's disease. Lancet. 1998;351:1330–1331
  32. Bertrand P, Guillaume D, Hellauer K, Dea D, Lindsay J, Kogan S, et al. Distribution of herpes simplex virus type 1 DNA in selected areas of normal and Alzheimer's disease brains: a PCR study. Neurodegeneration. 1993;2:201–208
  33. Valyi-Nagy T, Olson SJ, Valyi-Nagy K, Montine TJ, Dermody TS. Herpes simplex virus type 1 latency in the murine nervous system is associated with oxidative damage to neurons. Virology. 2000;278:309–321
  34. Wozniak MA, Itzhaki RF, Shipley SJ, Dobson CB. Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett. 2007;429:95–100
  35. Denaro FJ, Staub P, Colmer J, Freed DM. Coexistence of Alzheimer disease neuropathology with herpes simplex encephalitis. Cell Mol Biol (Noisy-le-Grand). 2003;49:1233–1240
  36. Corder E, Lannfelt L, Mulder M. Apolipoprotein E and herpes simplex virus 1 in Alzheimer's disease. Lancet. 1998;352:1312–1313
  37. Itabashi S, Arai H, Matsui T, Higuchi S, Sasaki H. Herpes simplex virus and risk of Alzheimer's disease. Lancet. 1997;349:1102
  38. Itzhaki RF, Lin WR, Wilcock GK, Faragher B. HSV-1 and risk of Alzheimer's disease. Lancet. 1998;352:238
  39. Itzhaki RF, Wozniak MA. Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer's disease and other disorders. Prog Lipid Res. 2006;45:73–90
  40. Isoniemi H, Tenovuo O, Portin R, Himanen L, Kairisto V. Outcome of traumatic brain injury after three decades—relationship to ApoE genotype. J Neurotrauma. 2006;23:1600–1608
  41. Corder EH, Robertson K, Lannfelt L, Bogdanovic N, Eggertsen G, Wilkins J, et al. HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy. Nat Med. 1998;4:1182–1184
  42. Slooter AJ, van Duijn CM. Genetic epidemiology of Alzheimer disease. Epidemiol Rev. 1997;19:107–119
  43. Oshima M, Azuma H, Suzutani T, Ikeda H, Okuno A. Direct and mononuclear cell mediated effects on interleukin 6 production by glioma cells in infection with herpes simplex virus type 1. J Med Virol. 2001;63:252–258
  44. Luterman JD, Haroutunian V, Yemul S, Ho L, Purohit D, Aisen PS, et al. Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol. 2000;57:1153–1160
  45. Huang LM, Lee CY, Lee PI, Chen JM, Wang PJ. Meningitis caused by human herpesvirus-6. Arch Dis Child. 1991;66:1443–1444
  46. McCullers JA, Lakeman FD, Whitley RJ. Human herpesvirus 6 is associated with focal encephalitis. Clin Infect Dis. 1995;21:571–576
  47. Luppi M, Barozzi P, Maiorana A, Marasca R, Torelli G. Human herpesvirus 6 infection in normal human brain tissue. J Infect Dis. 1994;169:943–944
  48. Qavi HB. Possible role of HHV-6 in the enhanced severity of HSV-1 keratitis. In Vivo. 1999;13:427–432
  49. Lin WR, Casas I, Wilcock GK, Itzhaki RF. Neurotropic viruses and Alzheimer's disease: a search for Varicella zoster virus DNA by the polymerase chain reaction. J Neurol Neurosurg Psychiatry. 1997;62:586–589
  50. Kittur SD, Hoh JH, Kawas CH, Hayward GS, Endo H, Adler WH. A molecular hybridization study for the presence of herpes simplex, cytomegalovirus and Epstein-Barr virus in brain and blood of Alzheimer's disease patients. Arch Gerontol Geriatr. 1992;15:35–41
  51. Wozniak MA, Shipley SJ, Dobson CB, Parker SP, Scott FT, Leedham-Green M, et al. Does apolipoprotein E determine outcome of infection by Varicella zoster virus and by Epstein Barr virus?. Eur J Hum Genet. 2007;15:672–678
  52. Volpi A. Epstein-Barr virus and human herpesvirus type 8 infections of the central nervous system. Herpes. 2004;11(Suppl. 2):120A–127A
  53. Feuer R, Mena I, Pagarigan RR, Harkins S, Hassett DE, Whitton JL. Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol. 2003;163:1379–1393
  54. Su W, Ueno-Yamanouchi A, Uetsuka K, Nakayama H, Doi K. Age-related changes in susceptibility of rat brain slice cultures including hippocampus to encephalomyocarditis virus. Int J Exp Pathol. 1999;80:349–355
  55. Buenz EJ, Rodriguez M, Howe CL. Disrupted spatial memory is a consequence of picornavirus infection. Neurobiol Dis. 2006;24:266–273
  56. Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001;58:1395–1402
  57. Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, et al. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol. 2006;63:665–672
  58. Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H. Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med. 1995;1:232–236
  59. Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, et al. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science. 1985;228:755–756
  60. Staeheli P, Sauder C, Hausmann J, Ehrensperger F, Schwemmle M. Epidemiology of Borna disease virus. J Gen Virol. 2000;81:2123–2135
  61. Dittrich W, Bode L, Ludwig H, Kao M, Schneider K. Learning deficiencies in Borna disease virus-infected but clinically healthy rats. Biol Psychiatry. 1989;26:818–828
  62. Sauder C, Wolfer DP, Lipp HP, Staeheli P, Hausmann J. Learning deficits in mice with persistent Borna disease virus infection of the CNS associated with elevated chemokine expression. Behav Brain Res. 2001;120:189–201
  63. Stahl T, Reimers C, Johne R, Schliebs R, Seeger J. Viral-induced inflammation is accompanied by beta-amyloid plaque reduction in brains of amyloid precursor protein transgenic Tg2576 mice. Eur J Neurosci. 2006;24:1923–1934
  64. Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, et al. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science. 2002;298:1379
  65. Wojtowicz WM, Farzan M, Joyal JL, Carter K, Babcock GJ, Israel DI, et al. Stimulation of enveloped virus infection by beta-amyloid fibrils. J Biol Chem. 2002;277:35019–35024
  66. Heinonen O, Syrjanen S, Mantyjarvi R, Syrjanen K, Riekkinen P. JC virus infection and Alzheimer's disease: reappraisal of an in situ hybridization approach. Ann Neurol. 1992;31:439–441
  67. Esiri MM, Biddolph SC, Morris CS. Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry. 1998;65:29–33
  68. Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS. 2005;19:127–135
  69. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS. 2005;19:407–411
  70. Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM. Chlamydia infections and heart disease linked through antigenic mimicry. Science. 1999;283:1335–1339
  71. Elkind MS, Tondella ML, Feikin DR, Fields BS, Homma S, Di Tullio MR. Seropositivity to Chlamydia pneumoniae is associated with risk of first ischemic stroke. Stroke. 2006;37:790–795
  72. Grayston JT, Aldous MB, Easton A, Wang SP, Kuo CC, Campbell LA, et al. Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J Infect Dis. 1993;168:1231–1235
  73. Wimmer ML, Sandmann-Strupp R, Saikku P, Haberl RL. Association of chlamydial infection with cerebrovascular disease. Stroke. 1996;27:2207–2210
  74. Capron L. Chlamydia in coronary plaques—hidden culprit or harmless hobo?. Nat Med. 1996;2:856–857
  75. Maass M, Bartels C, Engel PM, Mamat U, Sievers HH. Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease. J Am Coll Cardiol. 1998;31:827–832
  76. Stassen FR, Vainas T, Bruggeman CA. Infection and atherosclerosis. An alternative view on an outdated hypothesis. Pharmacol Rep. 2008;60:85–92
  77. Gerard HC, Dreses-Werringloer U, Wildt KS, Deka S, Oszust C, Balin BJ, et al. Chlamydophila (Chlamydia) pneumoniae in the Alzheimer's brain. FEMS Immunol Med Microbiol. 2006;48:355–366
  78. Gerard HC, Wildt KL, Whittum-Hudson JA, Lai Z, Ager J, Hudson AP. The load of Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype. Microb Pathog. 2005;39:19–26
  79. Gieffers J, Reusche E, Solbach W, Maass M. Failure to detect Chlamydia pneumoniae in brain sections of Alzheimer's disease patients. J Clin Microbiol. 2000;38:881–882
  80. Nochlin D, Shaw CM, Campbell LA, Kuo CC. Failure to detect Chlamydia pneumoniae in brain tissues of Alzheimer's disease. Neurology. 1999;53:1888
  81. Little CS, Hammond CJ, MacIntyre A, Balin BJ, Appelt DM. Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice. Neurobiol Aging. 2004;25:419–429
  82. Forloni G, Colombo L, Girola L, Tagliavini F, Salmona M. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 2001;487:404–407
  83. Tomiyama T, Shoji A, Kataoka K, Suwa Y, Asano S, Kaneko H, et al. Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J Biol Chem. 1996;271:6839–6844
  84. Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, et al. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J Am Geriatr Soc. 2004;52:381–387
  85. Verhoeff N. Do NSAIDs reduce the risk of developing AD?. CAGP Bull. 2003;10:14–15
  86. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311–1315
  87. Howden CW. Clinical expressions of Helicobacter pylori infection. Am J Med. 1996;100(Suppl.):27S–32S
  88. Kountouras J, Deretzi G, Zavos C, Karatzoglou P, Touloumis L, Nicolaides T, et al. Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2005;12:139–143
  89. Kountouras J, Mylopoulos N, Chatzopoulos D, Zavos C, Boura P, Konstas AG, et al. Eradication of Helicobacter pylori may be beneficial in the management of chronic open-angle glaucoma. Arch Intern Med. 2002;162:1237–1244
  90. Malaguarnera M, Bella R, Alagona G, Ferri R, Carnemolla A, Pennisi G. Helicobacter pylori and Alzheimer's disease: a possible link. Eur J Intern Med. 2004;15:381–386
  91. McCaddon A, Davies G, Hudson P. Nutritionally independent B12 deficiency and Alzheimer disease. Arch Neurol. 2000;57:607–608
  92. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346:476–483
  93. Grau AJ, Buggle F, Lichy C, Brandt T, Becher H, Rudi J. Helicobacter pylori infection as an independent risk factor for cerebral ischemia of atherothrombotic origin. J Neurol Sci. 2001;186:1–5
  94. Heuschmann PU, Neureiter D, Gesslein M, Craiovan B, Maass M, Faller G, et al. Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: results from a population-based case-control study. Stroke. 2001;32:2253–2258
  95. Markus HS, Mendall MA. Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma. J Neurol Neurosurg Psychiatry. 1998;64:104–107
  96. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002;52:168–174
  97. Bayer AU, Ferrari F, Erb C. High occurrence rate of glaucoma among patients with Alzheimer's disease. Eur Neurol. 2002;47:165–168
  98. Tamura H, Kawakami H, Kanamoto T, Kato T, Yokoyama T, Sasaki K, et al. High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease. J Neurol Sci. 2006;246:79–83
  99. Sugiyama T, Utsunomiya K, Ota H, Ogura Y, Narabayashi I, Ikeda T. Comparative study of cerebral blood flow in patients with normal-tension glaucoma and control subjects. Am J Ophthalmol. 2006;141:394–396
  100. Riviere GR, Riviere KH, Smith KS. Molecular and immunological evidence of oral treponema in the human brain and their association with Alzheimer's disease. Oral Microbiol Immunol. 2002;17:113–118
  101. Miklossy J, Kis A, Radenovic A, Miller L, Forro L, Martins R, et al. Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes. Neurobiol Aging. 2006;27:228–236
  102. McLaughlin R, Kin NM, Chen MF, Nair NP, Chan EC. Alzheimer's disease may not be a spirochetosis. Neuroreport. 1999;10:1489–1491
  103. Itzhaki RF, Wozniak MA, Appelt DM, Balin BJ. Infiltration of the brain by pathogens causes Alzheimer's disease. Neurobiol Aging. 2004;25:619–627
  104. Tyas SL, Manfreda J, Strain LA, Montgomery PR. Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada. Int J Epidemiol. 2001;30:590–597
  105. Verreault R, Laurin D, Lindsay J, De Serres G. Past exposure to vaccines and subsequent risk of Alzheimer's disease. Can Med Assoc J. 2001;165:1495–1498
  106. Hill AB. The environment and disease: association or causation?. Proc R Soc Med. 1965;58:295–300
  107. van Reekum R, Streiner DL, Conn DK. Applying Bradford Hill's criteria for causation to neuropsychiatry: challenges and opportunities. J Neuropsychiatry Clin Neurosci. 2001;13:318–325
  108. Itzhaki RF, Wozniak M, Dobson C, Lin WR. ApoE-viral interactions. Nat Med. 1998;4:1344
  109. Burgos JS, Ramirez C, Sastre I, Valdivieso F. Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA. J Virol. 2006;80:5383–5387
  110. Pratico D. Peripheral biomarkers of oxidative damage in Alzheimer's disease: the road ahead. Neurobiol Aging. 2005;26:581–583
  111. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer's disease: possible role of periodontal diseases. Alzheimers Dement. 2008;4:242–250
  112. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, et al. Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology. 2007;68:1902–1908
  113. DeKosky ST, Ikonomovic MD, Wang X, Farlow M, Wisniewski S, Lopez OL, et al. Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's disease: correlation with cognitive impairment. Ann Neurol. 2003;53:81–90
  114. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56:387–437
  115. Jang JH, Surh YJ. Beta-amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase-NF-kappaB signaling pathway. Free Radic Biol Med. 2005;38:1604–1613
  116. Gebhardt BM, Varnell ED, Kaufman HE. Inhibition of cyclooxygenase 2 synthesis suppresses herpes simplex virus type 1 reactivation. J Ocul Pharmacol Ther. 2005;21:114–120
  117. Soininen H, West C, Robbins J, Niculescu L. Long-term efficacy and safety of celecoxib in Alzheimer's disease. Dement Geriatr Cogn Disord. 2007;23:8–21
  118. Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC. Impact of APOE in mild cognitive impairment. Neurology. 2004;63:1898–1901

PII: S1552-5260(08)02983-X

doi: 10.1016/j.jalz.2008.12.001

Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 5, Issue 4 , Pages 348-360 , July 2009

Article Tools