Detection of α-Synuclein in Biological Samples Using Mass Spectrometry

  • Ann Brinkmalm
  • Annika Öhrfelt
  • Payel Bhattacharjee
  • Henrik ZetterbergEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1948)


Here we describe a method using mass spectrometry to characterize and quantify immuno-enriched α-synuclein forms from biochemically fractionated brain tissue.

Key words

Parkinson’s disease α-Synuclein Mass spectrometry CSF Brain 



Work in the authors’ laboratories is supported by the Michael J. Fox Foundation (MJFF) for Parkinson’s Research, the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Torsten Söderberg Foundation, the Eivind and Elsa K:Son Sylvans Foundation, the Märtha and Gustaf Ågrens Foundation, the Olav Thon Foundation, Swedish State Support for Clinical Research (ALFGBG), Alzheimerfonden, Stiftelsen för Gamla Tjänarinnor, and Frimurarestiftelsen.


  1. 1.
    Mollenhauer B, El-Agnaf OM, Marcus K, Trenkwalder C, Schlossmacher MG (2010) Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med 4(5):683–699CrossRefGoogle Scholar
  2. 2.
    Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA (2009) The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66(2):200–208CrossRefGoogle Scholar
  3. 3.
    Hall S, Ohrfelt A, Constantinescu R, Andreasson U, Surova Y, Bostrom F et al (2012) Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol 69(11):1445–1452CrossRefGoogle Scholar
  4. 4.
    Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Doring F, Trenkwalder C, Schlossmacher MG (2011) Alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10(3):230–240CrossRefGoogle Scholar
  5. 5.
    Ohrfelt A, Grognet P, Andreasen N, Wallin A, Vanmechelen E, Blennow K et al (2009) Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett 450(3):332–335CrossRefGoogle Scholar
  6. 6.
    Slaets S, Vanmechelen E, Le Bastard N, Decraemer H, Vandijck M, Martin JJ et al (2014) Increased CSF alpha-synuclein levels in Alzheimer’s disease: correlation with tau levels. Alzheimers Dement 10(5 Suppl):S290–S298CrossRefGoogle Scholar
  7. 7.
    Tateno F, Sakakibara R, Kawai T, Kishi M, Murano T (2012) Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. Alzheimer Dis Assoc Disord 26(3):213–216CrossRefGoogle Scholar
  8. 8.
    Wennstrom M, Surova Y, Hall S, Nilsson C, Minthon L, Bostrom F et al (2013) Low CSF levels of both alpha-synuclein and the alpha-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PLoS One 8(1):e53250CrossRefGoogle Scholar
  9. 9.
    Kapaki E, Paraskevas GP, Emmanouilidou E, Vekrellis K (2013) The diagnostic value of CSF alpha-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer’s disease. PLoS One 8(11):e81654CrossRefGoogle Scholar
  10. 10.
    Oeckl P, Metzger F, Nagl M, von Arnim CA, Halbgebauer S, Steinacker P et al (2016) Alpha-, beta-, and gamma-synuclein quantification in cerebrospinal fluid by multiple reaction monitoring reveals increased concentrations in Alzheimer’s and Creutzfeldt-Jakob disease but no alteration in synucleinopathies. Mol Cell Proteomics 15(10):3126–3138CrossRefGoogle Scholar
  11. 11.
    Hansson O, Hall S, Ohrfelt A, Zetterberg H, Blennow K, Minthon L et al (2014) Levels of cerebrospinal fluid alpha-synuclein oligomers are increased in Parkinson’s disease with dementia and dementia with Lewy bodies compared to Alzheimer’s disease. Alzheimers Res Ther 6(3):25CrossRefGoogle Scholar
  12. 12.
    Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T et al (2010) Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75(20):1766–1772CrossRefGoogle Scholar
  13. 13.
    Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J, Christie S et al (2016) Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol 3(10):812–818CrossRefGoogle Scholar
  14. 14.
    Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder C et al (2017) Development of a biochemical diagnosis of Parkinson disease by detection of alpha-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol 74(2):163–172CrossRefGoogle Scholar
  15. 15.
    Barbour R, Kling K, Anderson JP, Banducci K, Cole T, Diep L et al (2008) Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis 5(2):55–59CrossRefGoogle Scholar
  16. 16.
    Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D et al (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133(Pt 3):713–726CrossRefGoogle Scholar
  17. 17.
    Uchihara T, Giasson BI (2016) Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. Acta Neuropathol 131(1):49–73CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Ann Brinkmalm
    • 1
  • Annika Öhrfelt
    • 1
  • Payel Bhattacharjee
    • 1
  • Henrik Zetterberg
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden
  2. 2.Clinical Neurochemistry LaboratorySahlgrenska University HospitalMölndalSweden
  3. 3.Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK
  4. 4.UK Dementia Research Institute at UCLLondonUK

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