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Clinical Aspects of Inflammation in Parkinson’s Disease

  • Madhavi Thomas
  • Christopher Adams
Chapter

Abstract

Inflammation in Parkinson’s disease (PD) is widely recognized as part of the pathologic process. Whether it is causative or contributory, remains under investigation. Current evidence shows chronic inflammation is now seen as a plausible mechanism of neurodegeneration in PD. Various biological markers such as cytokines, antibodies to alpha-synuclein, and peripheral T-cell changes have been shown in literature. Furthermore, comorbidity studies, genome-wide association studies, and other epidemiological studies have corroborated a role for inflammation in the initiation or progression of PD. Development and validation of inflammatory biomarkers in PD are still in the preliminary stages. However, it is important to review the potential markers so we can explore further possibilities. This review focuses on current evidence presented in various clinical studies starting with cytokine and other biologic markers and epidemiological studies that broaden our understanding of the role of in vivo inflammatory mechanisms in PD.

Keywords

Migration Inhibitory Factor Nonaspirin NSAID Unstimulated Peripheral Blood Mononuclear Cell Single Central Nervous System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5:463–6.PubMedCentralPubMedGoogle Scholar
  2. 2.
    Czirr E, Wyss-Coray T. The immunology of neurodegeneration. J Clin Invest. 2012;122:1156–63.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Ton TG, Jain S, Biggs ML, Thacker EL, Strotmeyer ES, Boudreau R, et al. Markers of inflammation in prevalent and incident Parkinson’s disease in the cardiovascular health study. Parkinsonism Relat Disord. 2012;18:274–8.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, et al. CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson’s disease. J Neuroimmune Pharmacol. 2012;7:927–38.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Fiszer U, Mix E, Fredrikson S, Kostulas V, Link H. Parkinson’s disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+ T cells in peripheral blood. Acta Neurol Scand. 1994;90:160–6.PubMedGoogle Scholar
  6. 6.
    Funk N, Wieghofer P, Grimm S, Schaefer R, Bühring HJ, Gasser T, et al. Characterization of peripheral hematopoietic stem cells and monocytes in Parkinson’s disease. Mov Disord. 2013;28:392–5.PubMedGoogle Scholar
  7. 7.
    Bongioanni P, Castagna M, Maltinti S, Boccardi B, Dadone F. T-lymphocyte tumor necrosis factor-alpha receptor binding in patients with Parkinson’s disease. J Neurol Sci. 1997;149(1):41–5.PubMedGoogle Scholar
  8. 8.
    Chiba S, Matsumoto H, Saitoh M, Kasahara M, Matsuya M, Kashiwagi M. A correlation study between serum adenosine deaminase activities and peripheral lymphocyte subsets in Parkinson’s disease. J Neurol Sci. 1995;132:170–3.PubMedGoogle Scholar
  9. 9.
    Fiszer U, Mix E, Fredrikson S, Kostulas V, Olsson T, Link H. Gamma delta+ T cells are increased in patients with Parkinson’s disease. J Neurol Sci. 1994;121:39–45.PubMedGoogle Scholar
  10. 10.
    Hisanaga K, Asagi M, Itoyama Y, Iwasaki Y. Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease. Arch Neurol. 2001;58:1580–3.PubMedGoogle Scholar
  11. 11.
    Munschauer FE, Stewart C, Jacobs L, Kaba S, Ghorishi Z, Greenberg SJ, et al. Circulating CD3+ CD4+ CD8+ T lymphocytes in multiple sclerosis. J Clin Immunol. 1993;13:113–8.PubMedGoogle Scholar
  12. 12.
    Berrih S, Gaud C, Bach MA, Le Brigand H, Binet JP, Bach JF. Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies. Clin Exp Immunol. 1981;45(1):1–8.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Stevens CH, Rowe D, Morel-Kopp MC, Orr C, Russell T, Ranola M, et al. Reduced T helper and B lymphocytes in Parkinson’s disease. J Neuroimmunol. 2012;252:95–9.PubMedGoogle Scholar
  14. 14.
    Kedmi M, Bar-Shira A, Gurevich T, Giladi N, Orr-Urtreger A. Decreased expression of B cell related genes in leukocytes of women with Parkinson’s disease. Mol Neurodegener. 2011;6:66.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, et al. Peripheral cytokines profile in Parkinson’s disease. Brain Behav Immun. 2009;23:55–63.PubMedGoogle Scholar
  16. 16.
    Bessler H, Djaldetti R, Salman H, Bergman M, Djaldetti M. IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson’s disease. Biomed Pharmacother. 1999;53:141–5.PubMedGoogle Scholar
  17. 17.
    Hasegawa Y, Inagaki T, Sawada M, Suzumura A. Impaired cytokine production by peripheral blood mononuclear cells and monocytes/macrophages in Parkinson’s disease. Acta Neurol Scand. 2000;101:159–64.PubMedGoogle Scholar
  18. 18.
    Klüter H, Vieregge P, Stolze H, Kirchner H. Defective production of interleukin-2 in patients with idiopathic Parkinson’s disease. J Neurol Sci. 1995;133:134–9.PubMedGoogle Scholar
  19. 19.
    Wandinger KP, Hagenah JM, Klüter H, Rothermundt M, Peters M, Vieregge P. Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson’s disease. J Neuroimmunol. 1999;98:214–20.PubMedGoogle Scholar
  20. 20.
    Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994;165:208–10.PubMedGoogle Scholar
  21. 21.
    Mount MP, Lira A, Grimes D, Smith PD, Faucher S, Slack R, et al. Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons. J Neurosci. 2007;27:3328–37.PubMedGoogle Scholar
  22. 22.
    Widner B, Leblhuber F, Fuchs D. Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease. J Neural Transm. 2002;109:181–9.PubMedGoogle Scholar
  23. 23.
    Fujishiro K, Hagihara M, Takahashi A, Nagatsu T. Concentrations of neopterin and biopterin in the cerebrospinal fluid of patients with Parkinson’s disease. Biochem Med Metab Biol. 1990;44:97–100.PubMedGoogle Scholar
  24. 24.
    Müller T, Blum-Degen D, Przuntek H, Kuhn W. Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson’s disease. Acta Neurol Scand. 1998;98:142–4.PubMedGoogle Scholar
  25. 25.
    Mogi M, Harada M, Narabayashi H, Inagaki H, Minami M, Nagatsu T. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson’s disease. Neurosci Lett. 1996;211:13–6.PubMedGoogle Scholar
  26. 26.
    Blum-Degen D, Müller T, Kuhn W, Gerlach M, Gerlach M, Przuntek H, Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett. 1995;202:17–20.PubMedGoogle Scholar
  27. 27.
    Qureshi GA, Baig S, Bednar I, Södersten P, Södersten P, Forsberg G, Siden A. Increased cerebrospinal fluid concentration of nitrite in Parkinson’s disease. Neuroreport. 1995;6:1642–4.PubMedGoogle Scholar
  28. 28.
    Kuiper MA, Visser JJ, Bergmans PL, Scheltens P, Wolters EC. Decreased cerebrospinal fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients. J Neurol Sci. 1994;121:46–9.PubMedGoogle Scholar
  29. 29.
    McRae Degueurce A, Gottfries CG, Karlsson I, Svennerholm L, Dahlström A. Antibodies in the CSF of a Parkinson patient recognizes neurons in rat mesencephalic regions. Acta Physiol Scand. 1986;126:313–5.PubMedGoogle Scholar
  30. 30.
    Marttila RJ, Rinne UK, Tiilikainen A. Virus antibodies in Parkinson’s disease. Herpes simplex and measles virus antibodies in serum and CSF and their relation to HLA types. J Neurol Sci. 1982;54:227–38.PubMedGoogle Scholar
  31. 31.
    Marttila RJ, Kalimo KO, Ziola BR, Halonen PE, Rinne UK. Herpes simplex virus subunit antibodies in patients with Parkinson’s disease. Arch Neurol. 1978;35:668–71.PubMedGoogle Scholar
  32. 32.
    Elizan TS, Madden DL, Noble GR, Herrmann KL, Gardner J, Schwartz J, et al. Viral antibodies in serum and CSF of Parkinsonian patients and controls. Arch Neurol. 1979;36:529–34.PubMedGoogle Scholar
  33. 33.
    Brodacki B, Staszewski J, Toczyłowska B, Kozłowska E, Drela N, Chalimoniuk M, et al. Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism. Neurosci Lett. 2008;441:158–62.PubMedGoogle Scholar
  34. 34.
    Dobbs RJ, Charlett A, Purkiss AG, Dobbs SM, Weller C, Peterson DW. Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand. 1999;100:34–41.PubMedGoogle Scholar
  35. 35.
    Scalzo P, Kümmer A, Cardoso F, Teixeira AL. Increased serum levels of soluble tumor necrosis factor-alpha receptor-1 in patients with Parkinson’s disease. J Neuroimmunol. 2009;216:122–5.PubMedGoogle Scholar
  36. 36.
    Devos D, Lebouvier T, Lardeux B, Biraud M, Rouaud T, Pouclet H, et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis. 2013;50:42–8.PubMedGoogle Scholar
  37. 37.
    Koziorowski D, Tomasiuk R, Szlufik S, Friedman A. Inflammatory cytokines and NT-proCNP in Parkinson’s disease patients. Cytokine. 2012;60(3):762–6.PubMedGoogle Scholar
  38. 38.
    Scalzo P, Kümmer A, Cardoso F, Teixeira AL. Serum levels of interleukin-6 are elevated in patients with Parkinson’s disease and correlate with physical performance. Neurosci Lett. 2010;468:56–8.PubMedGoogle Scholar
  39. 39.
    Hofmann KW, Schuh AF, Saute J, Townsend R, Fricke D, Leke R, et al. Interleukin-6 serum levels in patients with Parkinson’s disease. Neurochem Res. 2009;34:1401–4.PubMedGoogle Scholar
  40. 40.
    Chen H, O’Reilly EJ, Schwarzschild MA, Ascherio A. Peripheral inflammatory biomarkers and risk of Parkinson’s disease. Am J Epidemiol. 2008;167:90–5.PubMedGoogle Scholar
  41. 41.
    Rentzos M, Nikolaou C, Andreadou E, Paraskevas GP, Rombos A, Zoga M, et al. Circulating interleukin-10 and interleukin-12 in Parkinson’s disease. Acta Neurol Scand. 2009;119:332–7.PubMedGoogle Scholar
  42. 42.
    Rentzos M, Nikolaou C, Andreadou E, Rentzos M, Nikolaou C, Andreadou E, et al. Circulating interleukin-15 and RANTES chemokine in Parkinson’s disease. Acta Neurol Scand. 2007;116:374–9.PubMedGoogle Scholar
  43. 43.
    Nicoletti A, Fagone P, Donzuso G, Mangano K, Dibilio V, Caponnetto S, et al. Parkinson’s disease is associated with increased serum levels of macrophage migration inhibitory factor. Cytokine. 2011;55:165–7.PubMedGoogle Scholar
  44. 44.
    Song IU, Kim JS, Chung SW, Lee KS. Is there an association between the level of high-sensitivity C-reactive protein and idiopathic Parkinson’s disease? A comparison of Parkinson’s disease patients, disease controls and healthy individuals. Eur Neurol. 2009;62:99–104.PubMedGoogle Scholar
  45. 45.
    Song IU, Chung SW, Kim JS, Lee KS. Association between high-sensitivity C-reactive protein and risk of early idiopathic Parkinson’s disease. Neurol Sci. 2011;32:31–4.PubMedGoogle Scholar
  46. 46.
    Andican G, Konukoglu D, Bozluolcay M, Bayülkem K, Firtiına S, Burcak G. Plasma oxidative and inflammatory markers in patients with idiopathic Parkinson’s disease. Acta Neurol Belg. 2012;112:155–9.PubMedGoogle Scholar
  47. 47.
    Lindqvist D, Kaufman E, Brundin L, Hall S, Surova Y, Hansson O. Non-motor symptoms in patients with Parkinson’s disease – correlations with inflammatory cytokines in serum. PLoS One. 2012;7:e47387.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Lindqvist D, Hall S, Surovac Y. Cerebrospinal fluid inflammatory markers in Parkinson’s disease – associations with depression, fatigue, and cognitive impairment. Brain Behav Immun. 2013;33:183–9.PubMedGoogle Scholar
  49. 49.
    Woulfe J, Hoogendoorn H, Tarnopolsky M, Muñoz DG. Monoclonal antibodies against Epstein–Barr virus cross-react with alpha-synuclein in human brain. Neurology. 2000;55:1398–401.PubMedGoogle Scholar
  50. 50.
    Espay AJ, Henderson KK. Postencephalitic parkinsonism and basal ganglia necrosis due to Epstein–Barr virus infection. Neurology. 2011;76:1529–30.PubMedGoogle Scholar
  51. 51.
    Han M, Nagele E, DeMarshall C, Acharya N, Nagele R. Diagnosis of Parkinson’s disease based on disease-specific autoantibody profiles in human sera. PLoS One. 2012;7:e32383.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Benkler M, Agmon-Levin N, Hassin-Baer S, Cohen OS, Ortega-Hernandez OD, Levy A, et al. Immunology, autoimmunity, and autoantibodies in Parkinson’s disease. Clin Rev Allergy Immunol. 2012;42:164–71.PubMedGoogle Scholar
  53. 53.
    Double KL, Rowe DB, Carew-Jones FM, Hayes M, Chan DK, Blackie J, et al. Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp Neurol. 2009;217:297–301.PubMedGoogle Scholar
  54. 54.
    Yanamandra K, Gruden MA, Casaite V, Meskys R, Forsgren L, Morozova-Roche LA, et al. α-Synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS One. 2011;6:e18513.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Papachroni KK, Ninkina N, Papapanagiotou A, Hadjigeorgiou GM, Xiromerisiou G, Papadimitriou A, et al. Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. J Neurochem. 2007;101:749–56.PubMedCentralPubMedGoogle Scholar
  56. 56.
    Besong-Agbo D, Wolf E, Jessen F, Oechsner M, Hametner E, Poewe W, et al. Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology. 2013;80:169–75.PubMedGoogle Scholar
  57. 57.
    Zappia M, Crescibene L, Bosco D, Arabia G, Nicoletti G, Bagalà A, et al. Anti-GM1 ganglioside antibodies in Parkinson’s disease. Acta Neurol Scand. 2002;106:54–7.PubMedGoogle Scholar
  58. 58.
    Wahner AD, Sinsheimer JS, Bronstein JM, Ritz B. Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch Neurol. 2007;64:836–40.PubMedGoogle Scholar
  59. 59.
    Nishimura M, Mizuta I, Mizuta E, Yamasaki S, Ohta M, Kaji R, et al. Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson’s disease. Neurosci Lett. 2001;311:1–4.PubMedGoogle Scholar
  60. 60.
    Krüger R, Hardt C, Tschentscher F, Jäckel S, Kuhn W, Müller T, et al. Genetic analysis of immunomodulating factors in sporadic Parkinson’s disease. J Neural Transm. 2000;107:553–62.PubMedGoogle Scholar
  61. 61.
    Nishimura M, Mizuta I, Mizuta E, Yamasaki S, Ohta M, Kuno S. Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson’s disease. Neurosci Lett. 2000;284:73–6.PubMedGoogle Scholar
  62. 62.
    Nishimura M, Kuno S, Kaji R, Yasuno K, Kawakami H. Glutathione-S-transferase-1 and interleukin-1beta gene polymorphisms in Japanese patients with Parkinson’s disease. Mov Disord. 2005;20:901–2.PubMedGoogle Scholar
  63. 63.
    Schulte T, Schöls L, Müller T, Woitalla D, Berger K, Krüger R. Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson’s disease. Neurosci Lett. 2002;326:70–2.PubMedGoogle Scholar
  64. 64.
    Arman A, Isik N, Coker A, Candan F, Becit KS, List EO. Association between sporadic Parkinson disease and interleukin-1 beta −511 gene polymorphisms in the Turkish population. Eur Cytokine Netw. 2010;21:116–21.PubMedGoogle Scholar
  65. 65.
    Zhou YT, Yang JF, Zhang YL, Wang XY, Chan P. Protective role of interlekin-1 alpha gene polymorphism in Chinese Han population with sporadic Parkinson’s disease. Neurosci Lett. 2008;445:23–5.PubMedGoogle Scholar
  66. 66.
    Wu YR, Chen CM, Hwang JC, Chen ST, Feng IH, Hsu HC, et al. Interleukin-1 alpha polymorphism has influence on late-onset sporadic Parkinson’s disease in Taiwan. J Neural Transm. 2007;114:1173–7.PubMedGoogle Scholar
  67. 67.
    Nie K, Zhang Y, Gan R, Wang L, Zhao J, Huang Z, et al. Polymorphisms in immune/inflammatory cytokine genes are related to Parkinson’s disease with cognitive impairment in the Han Chinese population. Neurosci Lett. 2013;541:111–5.PubMedGoogle Scholar
  68. 68.
    Li D, He Q, Li R, Xu X, Chen B, Xie A. Interleukin-10 promoter polymorphisms in Chinese patients with Parkinson’s disease. Neurosci Lett. 2012;513:183–6.PubMedGoogle Scholar
  69. 69.
    Håkansson A, Westberg L, Nilsson S, Buervenich S, Carmine A, Holmberg B, et al. Investigation of genes coding for inflammatory components in Parkinson’s disease. Mov Disord. 2005;20:569–73.PubMedGoogle Scholar
  70. 70.
    Xu X, Li D, He Q, Gao J, Chen B, Xie A. Interleukin-18 promoter polymorphisms and risk of Parkinson’s disease in a Han Chinese population. Brain Res. 2011;1381:90–4.PubMedGoogle Scholar
  71. 71.
    Ross OA, O’Neill C, Rea IM, Lynch T, Gosal D, Wallace A, et al. Functional promoter region polymorphism of the proinflammatory chemokine IL-8 gene associates with Parkinson’s disease in the Irish. Hum Immunol. 2004;65:340–6.PubMedGoogle Scholar
  72. 72.
    Bialecka M, Kurzawski M, Klodowska-Duda G, Opala G, Juzwiak S, Kurzawski G, et al. CARD15 variants in patients with sporadic Parkinson’s disease. Neurosci Res. 2007;57:473–6.PubMedGoogle Scholar
  73. 73.
    Appenzeller S, Thier S, Papengut F, Klein C, Hagenah J, Kasten M, et al. No association between NOD2 variants and Parkinson’s disease. Mov Disord. 2012;27:1191–2.PubMedGoogle Scholar
  74. 74.
    Ahmed I, Tamouza R, Delord M, Krishnamoorthy R, Tzourio C, Mulot C, et al. Association between Parkinson’s disease and the HLA-DRB1 locus. Mov Disord. 2012;27:1104–10.PubMedGoogle Scholar
  75. 75.
    Saiki M, Baker A, Williams-Gray CH, Foltynie T, Goodman RS, Taylor CJ, et al. Association of the human leucocyte antigen region with susceptibility to Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2010;81:890–1.PubMedGoogle Scholar
  76. 76.
    International Parkinson Disease Genomics Consortium, Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377:641–9.PubMedGoogle Scholar
  77. 77.
    Puschmann A, Verbeeck C, Heckman MG, Soto-Ortolaza AI, Lynch T, Jasinska-Myga B, et al. Human leukocyte antigen variation and Parkinson’s disease. Parkinsonism Relat Disord. 2011;17:376–8.PubMedCentralPubMedGoogle Scholar
  78. 78.
    Guo Y, Deng X, Zheng W, Xu H, Song Z, Liang H, et al. HLA rs3129882 variant in Chinese Han patients with late-onset sporadic Parkinson disease. Neurosci Lett. 2011;501:185–7.PubMedGoogle Scholar
  79. 79.
    Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42:781–5.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013;136:28–42.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Lolekha P, Phanthumchinda K, Bhidayasiri R. Prevalence and risk factors of Parkinson’s disease in retired Thai traditional boxers. Mov Disord. 2010;25:1895–901.PubMedGoogle Scholar
  82. 82.
    Goldman SM, Tanner CM, Oakes D, Bhudhikanok GS, Gupta A, Langston JW. Head injury and Parkinson’s disease risk in twins. Ann Neurol. 2006;60:65–72.PubMedGoogle Scholar
  83. 83.
    Bower JH, Maraganore DM, Peterson BJ, McDonnell SK, Ahlskog JE, Rocca WA. Head trauma preceding PD: a case–control study. Neurology. 2003;60:1610–5.PubMedGoogle Scholar
  84. 84.
    Wu XF, Block ML, Zhang W, Qin L, Wilson B, Zhang WQ, et al. The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid Redox Signal. 2005;7:654–61.PubMedGoogle Scholar
  85. 85.
    Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119:866–72.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Tanner CM, Ross GW, Jewell SA, Hauser RA, Jankovic J, Factor SA, et al. Occupation and risk of parkinsonism: a multicenter case–control study. Arch Neurol. 2009;66:1106–13.PubMedGoogle Scholar
  87. 87.
    Kamel F, Tanner C, Umbach D, Hoppin J, Alavanja M, Blair A, et al. Pesticide exposure and self-reported Parkinson’s disease in the agricultural health study. Am J Epidemiol. 2007;165:364–74.PubMedGoogle Scholar
  88. 88.
    Firestone JA, Smith-Weller T, Franklin G, Swanson P, Longstreth Jr WT, Checkoway H. Pesticides and risk of Parkinson disease: a population-based case–control study. Arch Neurol. 2005;62:91–5.PubMedGoogle Scholar
  89. 89.
    Dhillon AS, Tarbutton GL, Levin JL, Plotkin GM, Lowry LK, Nalbone JT, et al. Pesticide/environmental exposures and Parkinson’s disease in East Texas. J Agromedicine. 2008;13:37–48.PubMedGoogle Scholar
  90. 90.
    Fukushima T, Tan X, Luo Y, Kanda H. Relationship between blood levels of heavy metals and Parkinson’s disease in China. Neuroepidemiology. 2010;34:18–24.PubMedGoogle Scholar
  91. 91.
    Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, et al. Occupational exposures to metals as risk factors for Parkinson’s disease. Neurology. 1997;48:650–8.PubMedGoogle Scholar
  92. 92.
    Gorell JM, Johnson CC, Rybicki BA. Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson’s disease. Neurotoxicology. 1999;20:239–47.PubMedGoogle Scholar
  93. 93.
    Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm. 2003;110:517–36.PubMedGoogle Scholar
  94. 94.
    Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One. 2011;6:e28032.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Nielsen HH, Qiu J, Friis S, Wermuth L, Ritz B. Treatment for Helicobacter pylori infection and risk of Parkinson’s disease in Denmark. Eur J Neurol. 2012;19:864–9.PubMedCentralPubMedGoogle Scholar
  96. 96.
    Fang F, Wirdefeldt K, Jacks A, Kamel F, Kamel F, Ye W, Chen H. CNS infections, sepsis and risk of Parkinson’s disease. Int J Epidemiol. 2012;41:1042–9.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Martyn CN. Infection in childhood and neurological diseases in adult life. Br Med Bull. 1997;53:24–39.PubMedGoogle Scholar
  98. 98.
    Martyn CN, Osmond C. Parkinson’s disease and the environment in early life. J Neurol Sci. 1995;132:201–6.PubMedGoogle Scholar
  99. 99.
    Pisani V, Stefani A, Pierantozzi M, Pisani V, Stefani A, Pierantozzi M, et al. Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease. J Neuroinflammation. 2012;9:188.PubMedCentralPubMedGoogle Scholar
  100. 100.
    Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de Vries R, de Klerk O, et al. Decreased blood–brain barrier P-glycoprotein function in the progression of Parkinson’s disease, PSP and MSA. J Neural Transm. 2008;115:1001–9.PubMedCentralPubMedGoogle Scholar
  101. 101.
    Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005;57:176–9.PubMedGoogle Scholar
  102. 102.
    Westerlund M, Belin AC, Anvret A, Håkansson A, Nissbrandt H, Lind C, et al. Association of a polymorphism in the ABCB1 gene with Parkinson’s disease. Parkinsonism Relat Disord. 2009;15:422–4.PubMedGoogle Scholar
  103. 103.
    Tan EK, Chan DK, Ng PW, Woo J, Teo YY, Tang K, et al. Effect of MDR1 haplotype on risk of Parkinson disease. Arch Neurol. 2005;62:460–4.PubMedGoogle Scholar
  104. 104.
    Lee CG, Tang K, Cheung YB, Lee CG, Tang K, Cheung YB, et al. MDR1, the blood–brain barrier transporter, is associated with Parkinson’s disease in ethnic Chinese. J Med Genet. 2004;41:e60.PubMedCentralPubMedGoogle Scholar
  105. 105.
    Rees K, Stowe R, Patel S, Ives N, Breen K, Clarke CE, et al. Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson’s disease: evidence from observational studies. Cochrane Database Syst Rev. 2011;11:CD008454.PubMedGoogle Scholar
  106. 106.
    Gao X, Chen H, Schwarzschild MA, Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurology. 2011;76:863–9.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Gagne JJ, Power MC. Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. Neurology. 2010;74:995–1002.PubMedCentralPubMedGoogle Scholar
  108. 108.
    Powers KM, Kay DM, Factor SA, Zabetian CP, Higgins DS, Samii A, et al. Combined effects of smoking, coffee, and NSAIDs on Parkinson’s disease risk. Mov Disord. 2008;23:88–95.PubMedGoogle Scholar
  109. 109.
    Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology. 2007;69:1836–42.PubMedGoogle Scholar
  110. 110.
    Hernán MA, Logroscino G, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology. 2006;66:1097–9.PubMedGoogle Scholar
  111. 111.
    Chen H, Zhang SM, Hernán MA, Schwarzschild MA, Willett WC, Colditz GA, et al. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol. 2003;60:1059–64.PubMedGoogle Scholar
  112. 112.
    Mutez E, Duhamel A, Defebvre L, Bordet R, Destée A, Kreisler A. Lipid-lowering drugs are associated with delayed onset and slower course of Parkinson’s disease. Pharmacol Res. 2009;60:41–5.PubMedGoogle Scholar
  113. 113.
    NINDS NET-PD Investigators. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006;66:664–71.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Madhavi Thomas
    • 1
    • 2
  • Christopher Adams
    • 1
  1. 1.North Texas Movement Disorders Institute, Inc.BedfordUSA
  2. 2.Department of NeurologyBaylor University Medical CenterDallasUSA

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