Skip to main content

Advertisement

SpringerLink
Log in

Global Protein Differential Expression Profiling of Cerebrospinal Fluid Samples Pooled from Chinese Sporadic CJD and non-CJD Patients

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The shotgun proteomic based on the approach of tandem mass tag (TMT) labeling has received increasing attention for neuroproteomics analysis and becomes an effective tool for the identification and quantification of a large number of proteins for the purpose of revealing key proteins involved in the neuronal dysfunction and an inflammatory response associated with neurodegenerative disorders. To assess the potential expression difference of proteins in cerebrospinal fluids (CSF) between Creutzfeldt–Jakob disease (CJD) and non-CJD patients, the pooled CSF samples from 39 Chinese probable sporadic CJD (sCJD) patients and from 52 non-CJD cases were comparably analyzed with the methodology of TMT labeling and RP-RP-UPLC-MS/MS. Totally, 437 possible proteins were identified in the tested CSF specimen, among them, 49 proteins with 95 % confidence interval. Differential assays showed among those 49 CSF proteins, 12 were upregulated and 13 were downregulated significantly in the sCJD compared to non-CJD. The most affected pathway of the differential expression proteins in CSF of sCJD was complement and coagulation cascade. Western blots for six selected changed proteins in the pooled CSF samples revealed the similar altering profiles in the groups of sCJD and non-CJD as proteomics. Furthermore, CSF samples from 24 CJD patients and 24 non-CJD patients were randomly selected and subjected individually into the Western blots of an increased protein (phosphoglycerate mutase 1) and a decreased one (alpha-1-antichymotrysin), which also confirmed the altering tendency of these identified proteins. Those data indicate that proteomic assay of CSF is a powerful technique not only for selection of the potential biomarkers for the development of diagnostic tool of CJD but also for supplement of useful scientific clues for understanding the CSF homeostasis during the pathogenesis of prion diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Prusiner SB, Scott MR, DeArmond SJ, Cohen FE (1998) Prion protein biology. Cell 93(3):337–348

    Article  CAS  PubMed  Google Scholar 

  2. Budka H, Aguzzi A, Brown P, Brucher JM, Bugiani O, Gullotta F, Haltia M, Hauw JJ, Ironside JW, Jellinger K et al (1995) Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5(4):459–466

    Article  CAS  PubMed  Google Scholar 

  3. Gary H, Kimbra K, Clarence JG, Kelvin HL, Michael GH (1996) The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 335:7

    Google Scholar 

  4. Weber T, Otto M, Bodemer M, Zerr I (1997) Diagnosis of Creutzfeldt-Jakob disease and related human spongiform encephalopathies. Biomed Pharmacother 51(9):381–387

    Article  CAS  PubMed  Google Scholar 

  5. WHO (2003) WHO manual for surveillance of human transmissible spongiform encephalopathies including variant Creutzfeldt-Jakob disease. WHO Communicable Disease Surveillance and Response

  6. Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U, Breithaupt M, Varges D, Meissner B, Ladogana A, Schuur M, Haik S, Collins SJ, Jansen GH, Stokin GB, Pimentel J, Hewer E, Collie D, Smith P, Roberts H, Brandel JP, van Duijn C, Pocchiari M, Begue C, Cras P, Will RG, Sanchez-Juan P (2009) Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 231:10

    Google Scholar 

  7. Van Everbroeck B, Boons J, Cras P (2005) Cerebrospinal fluid biomarkers in Creutzfeldt-Jakob disease. Clin Neurol Neurosurg 107(5):355–360

    Article  PubMed  Google Scholar 

  8. Pennington C, Chohan G, Mackenzie J, Andrews M, Will R, Knight R, Green A (2009) The role of cerebrospinal fluid proteins as early diagnostic markers for sporadic Creutzfeldt-Jakob disease. Neurosci Lett 455(1):56–59

    Article  CAS  PubMed  Google Scholar 

  9. Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58(2):192–197

    Article  CAS  PubMed  Google Scholar 

  10. Jesse S, Steinacker P, Cepek L, von Arnim CA, Tumani H, Lehnert S, Kretzschmar HA, Baier M, Otto M (2009) Glial fibrillary acidic protein and protein S-100B: different concentration pattern of glial proteins in cerebrospinal fluid of patients with Alzheimer’s disease and Creutzfeldt-Jakob disease. J Alzheimers Dis 17(3):541–551

    CAS  PubMed  Google Scholar 

  11. Chen C, Shi Q, Zhang BY, Wang GR, Zhou W, Gao C, Tian C, Mei GY, Han YL, Han J, Dong XP (2010) The prepared tau exon-specific antibodies revealed distinct profiles of tau in CSF of the patients with Creutzfeldt-Jakob disease. PLoS One 5(7):e11886

    Article  PubMed Central  PubMed  Google Scholar 

  12. Guntert A, Campbell J, Saleem M, O’Brien DP, Thompson AJ, Byers HL, Ward MA, Lovestone S (2010) Plasma gelsolin is decreased and correlates with rate of decline in Alzheimer’s disease. J Alzheimers Dis 21(2):585–596

    PubMed  Google Scholar 

  13. Zhang K, Schrag M, Crofton A, Trivedi R, Vinters H, Kirsch W (2012) Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics 12(8):1261–1268

    Article  CAS  PubMed  Google Scholar 

  14. Thompson A, Schafer J, Kuhn K, Kienle S, Schwarz J, Schmidt G, Neumann T, Johnstone R, Mohammed AK, Hamon C (2003) Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 75(8):1895–1904

    Article  CAS  PubMed  Google Scholar 

  15. Dayon L, Hainard A, Licker V, Turck N, Kuhn K, Hochstrasser DF, Burkhard PR, Sanchez JC (2008) Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. Anal Chem 80(8):2921–2931

    Article  CAS  PubMed  Google Scholar 

  16. Li Z, Adams RM, Chourey K, Hurst GB, Hettich RL, Pan C (2012) Systematic comparison of label-free, metabolic labeling, and isobaric chemical labeling for quantitative proteomics on LTQ Orbitrap Velos. J Proteome Res 11(3):1582–1590

    Article  CAS  PubMed  Google Scholar 

  17. Chen C, Xiao D, Zhou W, Zhang YC, Shi Q, Tian C, Zhang J, Zhou CX, Zhang JZ, Dong XP (2012) Comparative peptidome analyses of the profiles of the peptides ranging from 1–10 KD in CSF samples pooled from probable sporadic CJD and non-CJD patients. Prion 6(1):46–51

    Article  PubMed Central  PubMed  Google Scholar 

  18. Gilar M, Olivova P, Daly AE, Gebler JC (2005) Orthogonality of separation in two-dimensional liquid chromatography. Anal Chem 77(19):6426–6434

    Article  CAS  PubMed  Google Scholar 

  19. Gilar M, Olivova P, Daly AE, Gebler JC (2005) Two-dimensional separation of peptides using RP-RP-HPLC system with different pH in first and second separation dimensions. J Sep Sci 28(14):1694–1703

    Article  CAS  PubMed  Google Scholar 

  20. Keller A, Nesvizhskii AI, Kolker E, Aebersold R (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 74(20):5383–5392

    Article  CAS  PubMed  Google Scholar 

  21. Huang da W, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler MW, Lane HC, Lempicki RA (2007) DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 35(Web Server issue):W169–W175

    Article  PubMed Central  PubMed  Google Scholar 

  22. da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  CAS  Google Scholar 

  23. Qualtieri A, Urso E, Le Pera M, Sprovieri T, Bossio S, Gambardella A, Quattrone A (2010) Proteomic profiling of cerebrospinal fluid in Creutzfeldt-Jakob disease. Expert Rev Proteomics 7(6):907–917

    Article  CAS  PubMed  Google Scholar 

  24. Salmona M, Capobianco R, Colombo L, De Luigi A, Rossi G, Mangieri M, Giaccone G, Quaglio E, Chiesa R, Donati MB, Tagliavini F, Forloni G (2005) Role of plasminogen in propagation of scrapie. J Virol 79(17):11225–11230

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Mays CE, Ryou C (2010) Plasminogen stimulates propagation of protease-resistant prion protein in vitro. FASEB J 24(12):5102–5112

    Article  CAS  PubMed  Google Scholar 

  26. Piubelli C, Fiorini M, Zanusso G, Milli A, Fasoli E, Monaco S, Righetti PG (2006) Searching for markers of Creutzfeldt-Jakob disease in cerebrospinal fluid by two-dimensional mapping. Proteomics 6(Suppl 1):S256–S261

    Article  PubMed  Google Scholar 

  27. Singh A, Beveridge AJ, Singh N (2011) Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders. PLoS One 6(3):e16804

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Miele G, Seeger H, Marino D, Eberhard R, Heikenwalder M, Stoeck K, Basagni M, Knight R, Green A, Chianini F, Wuthrich RP, Hock C, Zerr I, Aguzzi A (2008) Urinary alpha1-antichymotrypsin: a biomarker of prion infection. PLoS One 3(12):e3870

    Article  PubMed Central  PubMed  Google Scholar 

  29. Quinn JF (2013) Biomarkers for Alzheimer’s disease: showing the way or leading us astray? J Alzheimers Dis 33(Suppl 1):S371–S376

    PubMed Central  PubMed  Google Scholar 

  30. Keeney JT, Swomley AM, Forster S, Harris JL, Sultana R, Butterfield DA (2013) Apolipoprotein A-I: insights from redox proteomics for its role in neurodegeneration. Proteomics Clin Appl 7(1–2):109–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Zerr I, Bodemer M, Racker S, Grosche S, Poser S, Kretzschmar HA, Weber T (1995) Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease. Lancet 345(8965):1609–1610

    Article  CAS  PubMed  Google Scholar 

  32. Kohira I, Tsuji T, Ishizu H, Takao Y, Wake A, Abe K, Kuroda S (2000) Elevation of neuron-specific enolase in serum and cerebrospinal fluid of early stage Creutzfeldt-Jakob disease. Acta Neurol Scand 102(6):385–387

    Article  CAS  PubMed  Google Scholar 

  33. Brechlin P, Jahn O, Steinacker P, Cepek L, Kratzin H, Lehnert S, Jesse S, Mollenhauer B, Kretzschmar HA, Wiltfang J, Otto M (2008) Cerebrospinal fluid-optimized two-dimensional difference gel electrophoresis (2-D DIGE) facilitates the differential diagnosis of Creutzfeldt-Jakob disease. Proteomics 8(20):4357–4366

    Article  CAS  PubMed  Google Scholar 

  34. Gawinecka J, Dieks J, Asif AR, Carimalo J, Heinemann U, Streich JH, Dihazi H, Schulz-Schaeffer W, Zerr I (2010) Codon 129 polymorphism specific cerebrospinal fluid proteome pattern in sporadic Creutzfeldt-Jakob disease and the implication of glycolytic enzymes in prion-induced pathology. J Proteome Res 9(11):5646–5657

    Article  CAS  PubMed  Google Scholar 

  35. Ulloa L, Montejo de Garcini E, Gomez-Ramos P, Moran MA, Avila J (1994) Microtubule-associated protein MAP1B showing a fetal phosphorylation pattern is present in sites of neurofibrillary degeneration in brains of Alzheimer’s disease patients. Brain Res Mol Brain Res 26(1–2):113–122

    Article  CAS  PubMed  Google Scholar 

  36. Gonzalez-Billault C, Jimenez-Mateos EM, Caceres A, Diaz-Nido J, Wandosell F, Avila J (2004) Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system. J Neurobiol 58(1):48–59

    Article  CAS  PubMed  Google Scholar 

  37. Xu G, Stevens SM Jr, Moore BD, McClung S, Borchelt DR (2013) Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-amyloidosis. Hum Mol Genet 22(14):2765–74

    Google Scholar 

  38. Zerr I, Bodemer M, Kaboth U, Kretzschmar H, Oellerich M, Armstrong VW (2004) Plasminogen activities and concentrations in patients with sporadic Creutzfeldt-Jakob disease. Neurosci Lett 371(2–3):163–166

    Article  CAS  PubMed  Google Scholar 

  39. Choe LH, Green A, Knight RS, Thompson EJ, Lee KH (2002) Apolipoprotein E and other cerebrospinal fluid proteins differentiate ante mortem variant Creutzfeldt-Jakob disease from ante mortem sporadic Creutzfeldt-Jakob disease. Electrophoresis 23(14):2242–2246

    Article  CAS  PubMed  Google Scholar 

  40. Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A (2000) Binding of disease-associated prion protein to plasminogen. Nature 408(6811):479–483

    Article  CAS  PubMed  Google Scholar 

  41. Maissen M, Roeckl C, Glatzel M, Goldmann W, Aguzzi A (2001) Plasminogen binds to disease-associated prion protein of multiple species. Lancet 357(9273):2026–2028

    Article  CAS  PubMed  Google Scholar 

  42. Ishii T, Haga S, Yagishita S, Tateishi J (1984) The presence of complements in amyloid plaques of Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker disease. Appl Pathol 2(6):370–379

    CAS  PubMed  Google Scholar 

  43. Klein MA, Kaeser PS, Schwarz P, Weyd H, Xenarios I, Zinkernagel RM, Carroll MC, Verbeek JS, Botto M, Walport MJ, Molina H, Kalinke U, Acha-Orbea H, Aguzzi A (2001) Complement facilitates early prion pathogenesis. Nat Med 7(4):488–492

    Article  CAS  PubMed  Google Scholar 

  44. Mabbott NA, Bruce ME, Botto M, Walport MJ, Pepys MB (2001) Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med 7(4):485–487

    Article  CAS  PubMed  Google Scholar 

  45. Erlich P, Dumestre-Perard C, Ling WL, Lemaire-Vieille C, Schoehn G, Arlaud GJ, Thielens NM, Gagnon J, Cesbron JY (2010) Complement protein C1q forms a complex with cytotoxic prion protein oligomers. J Biol Chem 285(25):19267–19276

    Article  CAS  PubMed  Google Scholar 

  46. Speth C, Dierich MP, Gasque P (2002) Neuroinvasion by pathogens: a key role of the complement system. Mol Immunol 38(9):669–679

    Article  CAS  PubMed  Google Scholar 

  47. Finehout EJ, Franck Z, Lee KH (2005) Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease. Dis Markers 21(2):93–101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Gasque P, Dean YD, McGreal EP, VanBeek J, Morgan BP (2000) Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology 49(1–2):171–186

    Article  CAS  PubMed  Google Scholar 

  49. Tuppo EE, Arias HR (2005) The role of inflammation in Alzheimer’s disease. Int J Biochem Cell Biol 37(2):289–305

    Article  CAS  PubMed  Google Scholar 

  50. Yamada T, McGeer PL, McGeer EG (1992) Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol 84(1):100–104

    Article  CAS  PubMed  Google Scholar 

  51. McGeer PL, McGeer EG (2004) Inflammation and neurodegeneration in Parkinson’s disease. Parkinsonism Relat Disord 10(Suppl 1):S3–S7

    Article  PubMed  Google Scholar 

  52. Sellebjerg F, Jaliashvili I, Christiansen M, Garred P (1998) Intrathecal activation of the complement system and disability in multiple sclerosis. J Neurol Sci 157(2):168–174

    Article  CAS  PubMed  Google Scholar 

  53. Kornek B, Lassmann H (2003) Neuropathology of multiple sclerosis—new concepts. Brain Res Bull 61(3):321–326

    Article  CAS  PubMed  Google Scholar 

  54. Tian C, Liu D, Chen C, Xu Y, Gong HS, Shi Q, Zhang BY, Han J, Dong XP (2013) Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease. Int J Mol Med 31(3):676–688

    CAS  PubMed  Google Scholar 

  55. Tian C, Liu D, Sun QL, Chen C, Xu Y, Wang H, Xiang W, Kretzschmar HA, Li W, Shi Q, Gao C, Zhang J, Zhang BY, Han J, Dong XP (2013) Comparative analysis of gene expression profiles between cortex and thalamus in Chinese fatal familial insomnia patients. Mol Neurobiol. doi:10.1007/s12035-013-8426-6

    Google Scholar 

  56. Kropp S, Zerr I, Schulz-Schaeffer WJ, Riedemann C, Bodemer M, Laske C, Kretzschmar HA, Poser S (1999) Increase of neuron-specific enolase in patients with Creutzfeldt-Jakob disease. Neurosci Lett 261(1–2):124–126

    Article  CAS  PubMed  Google Scholar 

  57. Fountoulakis M, Cairns N, Lubec G (1999) Increased levels of 14-3-3 gamma and epsilon proteins in brain of patients with Alzheimer’s disease and Down syndrome. J Neural Transm Suppl 57:323–335

    CAS  PubMed  Google Scholar 

  58. Singh A, Isaac AO, Luo X, Mohan ML, Cohen ML, Chen F, Kong Q, Bartz J, Singh N (2009) Abnormal brain iron homeostasis in human and animal prion disorders. PLoS Pathog 5(3):e1000336

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the China Mega-Project for Infectious Disease (2011ZX10004-101, 2012ZX10004215), Chinese National Natural Science Foundation Grants (81100980), Young Scholar Scientific Research Foundation of China CDC (2012A102), and the SKLID Development Grant (2012SKLID102, 2011SKLID104 and 2011SKLID211).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center of Infectious Disease, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China

    Cao Chen, Wei Zhou, Qi Shi, Jin Zhang, Chan Tian & Xiao-Ping Dong

  2. State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China

    Di Xiao, Hui-Fang Zhang & Jian-Zhong Zhang

  3. Chinese Academy of Sciences, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China

    Xiao-Ping Dong

Authors
  1. Cao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Di Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qi Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui-Fang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chan Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-Zhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiao-Ping Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jian-Zhong Zhang or Xiao-Ping Dong.

Additional information

Authors Cao Chen and Di Xiao contributed equally to this work.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 671 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, C., Xiao, D., Zhou, W. et al. Global Protein Differential Expression Profiling of Cerebrospinal Fluid Samples Pooled from Chinese Sporadic CJD and non-CJD Patients. Mol Neurobiol 49, 290–302 (2014). https://doi.org/10.1007/s12035-013-8519-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-013-8519-2

Keywords

Search

Navigation