Neuroproteomics: The Methods

  • Ka Wan LiEmail author
Part of the Neuromethods book series (NM, volume 146)


Neuroproteomics is a branch of proteomics that analyses the (sub-)proteomes of the nervous system qualitatively or quantitatively. This chapter introduces the various methodologies that are commonly used in neuroproteomics research.


Nervous system Proteomics Mass spectrometer 


  1. 1.
    Lepeta K, Lourenco MV, Schweitzer BC, Martino Adami PV, Banerjee P, Catuara-Solarz S, de La Fuente Revenga M, Guillem AM, Haidar M, Ijomone OM, Nadorp B, Qi L, Perera ND, Refsgaard LK, Reid KM, Sabbar M, Sahoo A, Schaefer N, Sheean RK, Suska A, Verma R, Vicidomini C, Wright D, Zhang XD, Seidenbecher C (2016) Synaptopathies: synaptic dysfunction in neurological disorders - a review from students to students. J Neurochem 138:785–805CrossRefGoogle Scholar
  2. 2.
    Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1:a006189CrossRefGoogle Scholar
  3. 3.
    Koopmans F, Ho JTC, Smit AB, Li KW (2018) Comparative analyses of data independent acquisition mass spectrometric approaches: DIA, WiSIM-DIA, and untargeted DIA. Proteomics 18(1):1700304CrossRefGoogle Scholar
  4. 4.
    Pandya NJ, Koopmans F, Slotman JA, Paliukhovich I, Houtsmuller AB, Smit AB, Li KW (2017) Correlation profiling of brain sub-cellular proteomes reveals co-assembly of synaptic proteins and subcellular distribution. Sci Rep 7:12107CrossRefGoogle Scholar
  5. 5.
    Sialana FJ, Gulyassy P, Majek P, Sjostedt E, Kis V, Muller AC, Rudashevskaya EL, Mulder J, Bennett KL, Lubec G (2016) Mass spectrometric analysis of synaptosomal membrane preparations for the determination of brain receptors, transporters and channels. Proteomics 16:2911–2920CrossRefGoogle Scholar
  6. 6.
    Counotte DS, Goriounova NA, Li KW, Loos M, van der Schors RC, Schetters D, Schoffelmeer AN, Smit AB, Mansvelder HD, Pattij T, Spijker S (2011) Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nat Neurosci 14:417–419CrossRefGoogle Scholar
  7. 7.
    Van den Oever MC, Goriounova NA, Li KW, Van der Schors RC, Binnekade R, Schoffelmeer AN, Mansvelder HD, Smit AB, Spijker S, De Vries TJ (2008) Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking. Nat Neurosci 11:1053–1058CrossRefGoogle Scholar
  8. 8.
    Heo S, Diering GH, Na CH, Nirujogi RS, Bachman JL, Pandey A, Huganir RL (2018) Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover. Proc Natl Acad Sci U S A 115:E3827–E3836CrossRefGoogle Scholar
  9. 9.
    Umoh ME, Dammer EB, Dai J, Duong DM, Lah JJ, Levey AI, Gearing M, Glass JD, Seyfried NT (2018) A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain. EMBO Mol Med 10:48–62CrossRefGoogle Scholar
  10. 10.
    Ping L, Duong DM, Yin L, Gearing M, Lah JJ, Levey AI, Seyfried NT (2018) Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s disease. Sci Data 5:180036CrossRefGoogle Scholar
  11. 11.
    Monti C, Colugnat I, Lopiano L, Chio A, Alberio T (2018) Network analysis identifies disease-specific pathways for Parkinson’s Disease. Mol Neurobiol 55:370–381CrossRefGoogle Scholar
  12. 12.
    Hondius DC, Eigenhuis KN, Morrema THJ, van der Schors RC, van Nierop P, Bugiani M, Li KW, Hoozemans JJM, Smit AB, Rozemuller AJM (2018) Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer’s disease. Acta Neuropathol Commun 6:46CrossRefGoogle Scholar
  13. 13.
    Hondius DC, van Nierop P, Li KW, Hoozemans JJ, van der Schors RC, van Haastert ES, van der Vies SM, Rozemuller AJ, Smit AB (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimer’s disease. Alzheimers Dement 12:654–668CrossRefGoogle Scholar
  14. 14.
    Suzuki T, Kametani K, Guo W, Li W (2018) Protein components of post-synaptic density lattice, a backbone structure for type I excitatory synapses. J Neurochem 144:390–407CrossRefGoogle Scholar
  15. 15.
    Datta S, Malhotra L, Dickerson R, Chaffee S, Sen CK, Roy S (2015) Laser capture microdissection: Big data from small samples. Histol Histopathol 30:1255–1269PubMedPubMedCentralGoogle Scholar
  16. 16.
    Drummond E, Nayak S, Faustin A, Pires G, Hickman RA, Askenazi M, Cohen M, Haldiman T, Kim C, Han X, Shao Y, Safar JG, Ueberheide B, Wisniewski T (2017) Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer’s disease. Acta Neuropathol 133:933–954CrossRefGoogle Scholar
  17. 17.
    Wong TH, Chiu WZ, Breedveld GJ, Li KW, Verkerk AJ, Hondius D, Hukema RK, Seelaar H, Frick P, Severijnen LA, Lammers GJ, Lebbink JH, van Duinen SG, Kamphorst W, Rozemuller AJ, Netherlands Brain Bank, Bakker EB, International Parkinsonism Genetics Network, Neumann M, Willemsen R, Bonifati V, Smit AB, van Swieten J (2014) PRKAR1B mutation associated with a new neurodegenerative disorder with unique pathology. Brain 137:1361–1373CrossRefGoogle Scholar
  18. 18.
    Chen N, van der Schors RC, Smit AB (2011) A 1D-PAGE/LC-ESI linear ion trap orbitrap MS approach for the analysis of synapse proteomes and synaptic protein complexes. In: Li KW (ed) Neuroproteomics. Humana Press, Totowa, NJ, pp 159–167CrossRefGoogle Scholar
  19. 19.
    Wisniewski JR, Zougman A, Nagaraj N, Mann M (2009) Universal sample preparation method for proteome analysis. Nat Methods 6:359–362CrossRefGoogle Scholar
  20. 20.
    Hughes CS, Foehr S, Garfield DA, Furlong EE, Steinmetz LM, Krijgsveld J (2014) Ultrasensitive proteome analysis using paramagnetic bead technology. Mol Syst Biol 10:757CrossRefGoogle Scholar
  21. 21.
    Chen N, Koopmans F, Gordon A, Paliukhovich I, Klaassen RV, van der Schors RC, Peles E, Verhage M, Smit AB, Li KW (2015) Interaction proteomics of canonical Caspr2 (CNTNAP2) reveals the presence of two Caspr2 isoforms with overlapping interactomes. Biochim Biophys Acta 1854:827–833CrossRefGoogle Scholar
  22. 22.
    Li KW, Chen N, Klemmer P, Koopmans F, Karupothula R, Smit AB (2012) Identifying true protein complex constituents in interaction proteomics: the example of the DMXL2 protein complex. Proteomics 12:2428–2432CrossRefGoogle Scholar
  23. 23.
    Pandya NJ, Klaassen RV, van der Schors RC, Slotman JA, Houtsmuller A, Smit AB, Li KW (2016) Group 1 metabotropic glutamate receptors 1 and 5 form a protein complex in mouse hippocampus and cortex. Proteomics 16:2698–2705CrossRefGoogle Scholar
  24. 24.
    Chen N, Pandya NJ, Koopmans F, Castelo-Szekelv V, van der Schors RC, Smit AB, Li KW (2014) Interaction proteomics reveals brain region-specific AMPA receptor complexes. J Proteome Res 13:5695–5706CrossRefGoogle Scholar
  25. 25.
    Liu F, Lossl P, Rabbitts BM, Balaban RS, Heck AJR (2018) The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes. Mol Cell Proteomics 17:216–232CrossRefGoogle Scholar
  26. 26.
    Liu F, Rijkers DT, Post H, Heck AJ (2015) Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nat Methods 12:1179–1184CrossRefGoogle Scholar
  27. 27.
    McAlister GC, Nusinow DP, Jedrychowski MP, Wuhr M, Huttlin EL, Erickson BK, Rad R, Haas W, Gygi SP (2014) MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal Chem 86:7150–7158CrossRefGoogle Scholar
  28. 28.
    Ludwig C, Gillet L, Rosenberger G, Amon S, Collins BC, Aebersold R (2018) Data-independent acquisition-based SWATH-MS for quantitative proteomics: a tutorial. Mol Syst Biol 14:e8126CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam NeuroscienceVrije Universiteit AmsterdamAmsterdamThe Netherlands

Personalised recommendations