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01-09-2018 | Original Paper

Cerebrospinal Fluid C-Reactive Protein in Parkinson’s Disease: Associations with Motor and Non-motor Symptoms

Authors: Hossein Sanjari Moghaddam, Zahra Valitabar, Amir Ashraf-Ganjouei, Mahtab Mojtahed Zadeh, Farzaneh Ghazi Sherbaf, Mohammad Hadi Aarabi

Published in: NeuroMolecular Medicine | Issue 3/2018

Abstract

Parkinson’ disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms. Eighty-four healthy controls (HCs) and 109 PD subjects were entered into this study. A significant correlation was observed between CSF CRP levels and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS part III) score and Montreal Cognitive Assessment (MoCA) score in PD patients. We found significant correlations between MoCA score and CSF CRP levels in female patients and between CSF CRP and MDS-UPDRS part III score and MoCA score in male patients. In linear regression, CSF CRP could predict 6.9 and 10% of changes in MDS-UPDRS part III score in all PD patients male PD patients, respectively. In summary, we confirmed that CSF concentrations of CRP are in correlation with motor and non-motor severity in PD subjects. Our findings suggest that neuroinflammation plays an important role in the initiation and probably progression of PD motor and non-motor symptoms, which may give us a better insight into the underlying pathologic mechanisms in PD.

Barnum, C. J., & Tansey, M. G. (2012). Neuroinflammation and non-motor symptoms: The dark passenger of Parkinson’s disease? Current Neurology and Neuroscience Reports, 12(4), 350–358. https://doi.org/10.1007/s11910-012-0283-6.CrossRefPubMed

Berczi, I., Quintanar-Stephano, A., & Kovacs, K. (2009) Neuroimmune regulation in immunocompetence, acute illness, and healing. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.2008.03975.x.PubMedCrossRef

Bordelon, Y. M., Hays, R. D., Vassar, S. D., Diaz, N., Bronstein, J., & Vickrey, B. G. (2011). Medication responsiveness of motor symptoms in a population-based study of Parkinson disease. Parkinson’s Disease, 2011, 967839. https://doi.org/10.4061/2011/967839.PubMedPubMedCentralCrossRef

Chen, H., O’Reilly, E. J., Schwarzschild, M. A., & Ascherio, A. (2008). Peripheral inflammatory biomarkers and risk of Parkinson’s disease. American Journal of Epidemiology, 167(1), 90–95. https://doi.org/10.1093/aje/kwm260.CrossRefPubMed

Closhen, D., Bender, B., Luhmann, H. J., & Kuhlmann, C. R. (2010). CSF CRP-induced levels of oxidative stress are higher in brain than aortic endothelial cells. Cytokine, 50(2), 117–120. https://doi.org/10.1016/j.cyto.2010.02.011.CrossRefPubMed

Codolo, G., Plotegher, N., Pozzobon, T., Brucale, M., Tessari, I., Bubacco, L., & de Bernard, M. (2013). Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS ONE, 8(1), e55375. https://doi.org/10.1371/journal.pone.0055375.CrossRefPubMedPubMedCentral

Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 46–56. https://doi.org/10.1038/nrn2297.CrossRefPubMedPubMedCentral

Desai, B. S., Monahan, A. J., Carvey, P. M., & Hendey, B. (2007). Blood-brain barrier pathology in Alzheimer’s and Parkinson’s disease: Implications for drug therapy. Cell Transplantation, 16(3), 285–299.CrossRefPubMed

Di Napoli, M., Godoy, D. A., Campi, V., Masotti, L., Smith, C. J., Jones, A. R. P., et al. (2012). C-reactive protein in intracerebral hemorrhage: Time course, tissue localization, and prognosis. Neurology, 79(7), 690–699. https://doi.org/10.1212/WNL.0b013e318264e3be.CrossRefPubMed

Dunn, A. J. (2006). Effects of cytokines and infections on brain neurochemistry. Clinical Neuroscience Research, 6(1–2), 52–68. https://doi.org/10.1016/j.cnr.2006.04.002.CrossRefPubMedPubMedCentral

Duong, T., Nikolaeva, M., & Acton, P. J. (1997). C-reactive protein-like immunoreactivity in the neurofibrillary tangles of Alzheimer’s disease. Brain Research, 749(1), 152–156.CrossRefPubMed

Dursun, E., Gezen-Ak, D., Hanagasi, H., Bilgic, B., Lohmann, E., Ertan, S., et al. (2015). The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer’s disease, mild cognitive impairment or Parkinson’s disease. Journal of Neuroimmunology, 283, 50–57. https://doi.org/10.1016/j.jneuroim.2015.04.014.CrossRefPubMed

Haghshomar, M., Rahmani, F., Hadi Aarabi, M., Shahjouei, S., Sobhani, S., & Rahmani, M. (2017). White matter changes correlates of peripheral neuroinflammation in patients with Parkinson's disease. Neuroscience. https://doi.org/10.1016/j.neuroscience.2017.10.050.PubMedCrossRef

Hanisch, U. K., & Kettenmann, H. (2007). Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience, 10(11), 1387–1394. https://doi.org/10.1038/nn1997.CrossRefPubMed

Hassin-Baer, S., Cohen, O. S., Vakil, E., Molshazki, N., Sela, B. A., Nitsan, Z., et al. (2011) Is C-reactive protein level a marker of advanced motor and neuropsychiatric complications in Parkinson’s disease? Journal of Neural Transmission, 118(4), 539–543. https://doi.org/10.1007/s00702-010-0535-z.CrossRefPubMed

Hirsch, E. C., Breidert, T., Rousselet, E., Hunot, S., Hartmann, A., & Michel, P. P. (2003). The role of glial reaction and inflammation in Parkinson’s disease. Annals of the New York Academy of Sciences, 991, 214–228.CrossRefPubMed

Hirsch, E. C., & Hunot, S. (2009). Neuroinflammation in Parkinson’s disease: A target for neuroprotection? The Lancet Neurology, 8(4), 382–397. https://doi.org/10.1016/s1474-4422(09)70062-6.CrossRefPubMed

Hirsch, E. C., Vyas, S., & Hunot, S. (2012). Neuroinflammation in Parkinson’s disease. Parkinsonism & Related Disorders, 18(Suppl 1), S210–S212. https://doi.org/10.1016/s1353-8020(11)70065-7.CrossRef

Iwamoto, N., Nishiyama, E., Ohwada, J., & Arai, H. (1994). Demonstration of CSF CRP immunoreactivity in brains of Alzheimer’s disease: Immunohistochemical study using formic acid pretreatment of tissue sections. Neuroscience Letters, 177(1–2), 23–26.CrossRefPubMed

Kang, U. J., Goldman, J. G., Alcalay, R. N., Xie, T., Tuite, P., Henchcliffe, C., et al. (2016). The BioFIND study: Characteristics of a clinically typical Parkinson’s disease biomarker cohort. Movement Disorders: Official Journal of the Movement Disorder Society, 31(6), 924–932. https://doi.org/10.1002/mds.26613.CrossRef

Koprich, J. B., Reske-Nielsen, C., Mithal, P., & Isacson, O. (2008). Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson’s disease. Journal of Neuroinflammation, 5, 8. https://doi.org/10.1186/1742-2094-5-8.CrossRefPubMedPubMedCentral

Li, Y. N., Qin, X. J., Kuang, F., Wu, R., Duan, X. L., Ju, G., & Wang, B. R. (2008). Alterations of Fc gamma receptor I and Toll-like receptor 4 mediate the antiinflammatory actions of microglia and astrocytes after adrenaline-induced blood-brain barrier opening in rats. Journal of Neuroscience Research, 86(16), 3556–3565. https://doi.org/10.1002/jnr.21810.CrossRefPubMed

Lindqvist, D., Hall, S., Surova, Y., Nielsen, H. M., Janelidze, S., Brundin, L., & Hansson, O. (2013). Cerebrospinal fluid inflammatory markers in Parkinson’s disease: Associations with depression, fatigue, and cognitive impairment. Brain, Behavior, and Immunity, 33, 183–189. https://doi.org/10.1016/j.bbi.2013.07.007.CrossRefPubMed

Lindqvist, D., Kaufman, E., Brundin, L., Hall, S., Surova, Y., & Hansson, O. (2012). Non-motor symptoms in patients with Parkinson’s disease: Correlations with inflammatory cytokines in serum. PLoS ONE, 7(10), e47387. https://doi.org/10.1371/journal.pone.0047387.CrossRefPubMedPubMedCentral

Litvan, I., Chesselet, M. F., Gasser, T., Di Monte, D. A., Parker, D. Jr., Hagg, T., et al. (2007). The etiopathogenesis of Parkinson disease and suggestions for future research. Part II. Journal of Neuropathology and Experimental Neurology, 66(5), 329–336. https://doi.org/10.1097/nen.0b013e318053716a.CrossRefPubMed

Lv, Y., Zhang, Z., Hou, L., Zhang, L., Zhang, J., Wang, Y., et al. (2015). Phytic acid attenuates inflammatory responses and the levels of NF-kappaB and p-ERK in MPTP-induced Parkinson’s disease model of mice. Neuroscience Letters, 597, 132–136. https://doi.org/10.1016/j.neulet.2015.04.040.CrossRefPubMed

McGeer, P. L., & McGeer, E. G. (1995). The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Research Reviews, 21(2), 195–218. https://doi.org/10.1016/0165-0173(95)00011-9.CrossRefPubMed

McGeer, P. L., & McGeer, E. G. (2004). Inflammation and neurodegeneration in Parkinson’s disease. Parkinsonism & Related Disorders, 10(Suppl 1), S3-7. https://doi.org/10.1016/j.parkreldis.2004.01.005.CrossRef

Menza, M., Dobkin, R. D., Marin, H., Mark, M. H., Gara, M., Bienfait, K., et al. (2010). The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson’s disease. Psychosomatics, 51(6), 474–479. https://doi.org/10.1176/appi.psy.51.6.474.PubMedPubMedCentralCrossRef

Nagatsu, T., & Sawada, M. (2005). Inflammatory process in Parkinson’s disease: Role for cytokines. Current Pharmaceutical Design, 11(8), 999–1016.CrossRefPubMed

Paul, A., Ko, K. W., Li, L., Yechoor, V., McCrory, M. A., Szalai, A. J., & Chan, L. (2004). C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation, 109(5), 647–655. https://doi.org/10.1161/01.cir.0000114526.50618.24.CrossRefPubMed

Pott Godoy, M. C., Ferrari, C. C., & Pitossi, F. J. (2010). Nigral neurodegeneration triggered by striatal AdIL-1 administration can be exacerbated by systemic IL-1 expression. Journal of Neuroimmunology, 222(1–2), 29–39. https://doi.org/10.1016/j.jneuroim.2010.02.018.CrossRefPubMed

Pott Godoy, M. C., Tarelli, R., Ferrari, C. C., Sarchi, M. I., & Pitossi, F. J. (2008). Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain: A Journal of Neurology, 131(Pt 7), 1880–1894. https://doi.org/10.1093/brain/awn101.CrossRef

Qin, X. Y., Zhang, S. P., Cao, C., Loh, Y. P., & Cheng, Y. (2016). Aberrations in peripheral inflammatory cytokine levels in Parkinson disease: A systematic review and meta-analysis. JAMA Neurology, 73(11), 1316–1324. https://doi.org/10.1001/jamaneurol.2016.2742.CrossRefPubMed

Rocha, N., Pessoa, l., de Miranda, A. S., & Teixeira, A. L. (2015). Insights into neuroinflammation in Parkinson’s disease: From biomarkers to anti-inflammatory based therapies. BioMed Research International, 2015, 12. https://doi.org/10.1155/2015/628192.CrossRef

Sanjari Moghaddam, H., Ghazi Sherbaf, F., Mojtahed Zadeh, M., Ashraf-Ganjouei, A., & Aarabi, M. H. (2018). Association between peripheral inflammation and DATSCAN data of the striatal nuclei in different motor subtypes of Parkinson disease. Frontiers in Neurology, 9, 234. https://doi.org/10.3389/fneur.2018.00234.CrossRefPubMedPubMedCentral

Scalzo, P., Kummer, A., Cardoso, F., & Teixeira, A. L. (2010). Serum levels of interleukin-6 are elevated in patients with Parkinson’s disease and correlate with physical performance. Neuroscience Letters, 468(1), 56–58. https://doi.org/10.1016/j.neulet.2009.10.062.CrossRefPubMed

Schiepers, O. J. G., Wichers, M. C., & Maes, M. (2005). Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29(2), 201–217. https://doi.org/10.1016/j.pnpbp.2004.11.003.CrossRefPubMed

Schmidt, R., Schmidt, H., Curb, J. D., Masaki, K., White, L. R., & Launer, L. J. (2002). Early inflammation and dementia: A 25-year follow-up of the Honolulu-Asia Aging Study. Annals of Neurology, 52(2), 168–174. https://doi.org/10.1002/ana.10265.CrossRefPubMed

Tan, Z. S., Beiser, A. S., Vasan, R. S., Roubenoff, R., Dinarello, C. A., Harris, T. B., et al. (2007). Inflammatory markers and the risk of Alzheimer disease: The Framingham Study. Neurology, 68(22), 1902–1908. https://doi.org/10.1212/01.wnl.0000263217.36439.da.CrossRefPubMed

Tansey, M. G., McCoy, M. K., & Frank-Cannon, T. C. (2007). Neuroinflammatory mechanisms in Parkinson’s disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention. Experimental Neurology, 208(1), 1–25. https://doi.org/10.1016/j.expneurol.2007.07.004.CrossRefPubMedPubMedCentral

Teismann, P., Tieu, K., Choi, D. K., Wu, D. C., Naini, A., Hunot, S., et al. (2003). Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America, 100(9), 5473–5478. https://doi.org/10.1073/pnas.0837397100.CrossRefPubMedPubMedCentral

Umemura, A., Oeda, T., Tomita, S., Hayashi, R., Kohsaka, M., Park, K., et al. (2014). Delirium and high fever are associated with subacute motor deterioration in Parkinson disease: a nested case-control study. PLoS ONE, 9(6), e94944. https://doi.org/10.1371/journal.pone.0094944.CrossRefPubMedPubMedCentral

Umemura, A., Oeda, T., Yamamoto, K., Tomita, S., Kohsaka, M., Park, K., et al. (2015). Baseline plasma C-reactive protein concentrations and motor prognosis in Parkinson disease. PLoS ONE, 10(8), e0136722. https://doi.org/10.1371/journal.pone.0136722.CrossRefPubMedPubMedCentral

Villaran, R. F., Espinosa-Oliva, A. M., Sarmiento, M., De Pablos, R. M., Arguelles, S., Delgado-Cortes, M. J., et al. (2010). Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: Potential risk factor in Parkinson`s disease. Journal of Neurochemistry, 114(6), 1687–1700. https://doi.org/10.1111/j.1471-4159.2010.06879.x.CrossRefPubMed

Yasojima, K., Schwab, C., McGeer, E. G., & McGeer, P. L. (2000). Human neurons generate C-reactive protein and amyloid P: Upregulation in Alzheimer’s disease. Brain Research, 887(1), 80–89. https://doi.org/10.1016/S0006-8993(00)02970-X.CrossRefPubMed

Yeh, E. T. H. (2005). A new perspective on the biology of C-reactive protein. Circulation Research, 97(7), 609–611. https://doi.org/10.1161/01.RES.0000186188.38344.13.CrossRefPubMed

Zhang, L., Yan, J., Xu, Y., Long, L., Zhu, C., Chen, X., et al. (2011). The combination of homocysteine and C-reactive protein predicts the outcomes of Chinese patients with Parkinson’s disease and vascular parkinsonism. PLoS ONE, 6(4), e19333. https://doi.org/10.1371/journal.pone.0019333.CrossRefPubMedPubMedCentral

Title: Cerebrospinal Fluid C-Reactive Protein in Parkinson’s Disease: Associations with Motor and Non-motor Symptoms
Authors: Hossein Sanjari Moghaddam
Zahra Valitabar
Amir Ashraf-Ganjouei
Mahtab Mojtahed Zadeh
Farzaneh Ghazi Sherbaf
Mohammad Hadi Aarabi
Publication date: 01-09-2018
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 3/2018
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-018-8499-5

At a glance: The STEP trials

Springer Medicine

Cerebrospinal Fluid C-Reactive Protein in Parkinson’s Disease: Associations with Motor and Non-motor Symptoms

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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