Abstract
Introduction
In autopsy cases staged for sporadic Parkinson’s disease (PD), the neuropathology is characterized by a preclinical phase that targets the enteric nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a source of potential (presymptomatic) PD biomarkers.
Methods
In this clinically based study, we examined the alpha-synuclein (αSyn) concentration in an easily accessible protein storage medium of the GIT, dental calculus, in 21/50 patients with PD and 28/50 age- and gender-matched controls using ELISA.
Results
αSyn was detectable in dental calculus and the median concentration in the control patients was 8.6 pg/mg calculus (interquartile range 2.6–13.1 pg/mg). αSyn concentrations were significantly influenced by blood contamination and samples with a hemoglobin concentration of > 4000 ng/mL were excluded. There was no significant difference of αSyn concentrations in the dental calculus of PD patients (5.76 pg/mg, interquartile range 2.91–9.74 pg/mg) compared to those in controls (p = 0.40).
Conclusion
The total αSyn concentration in dental calculus is not a suitable biomarker for sporadic PD. Disease-related variants such as oligomeric or phosphorylated αSyn in calculus might prove to be more specific.
Similar content being viewed by others
References
Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912. https://doi.org/10.1016/S0140-6736(14)61393-3
Halbgebauer S, Öckl P, Wirth K et al (2016) Protein biomarkers in Parkinson’s disease: focus on cerebrospinal fluid markers and synaptic proteins. Mov Disord 31:848–860. https://doi.org/10.1002/mds.26635
Braak H, de Vos RAI, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72. https://doi.org/10.1016/j.neulet.2005.11.012
Del Tredici K, Hawkes CH, Ghebremedhin E, Braak H (2010) Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol 119:703–713. https://doi.org/10.1007/s00401-010-0665-2
Braak H, Rüb U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110:517–536. https://doi.org/10.1007/s00702-002-0808-2
Lionnet A, Leclair-Visonneau L, Neunlist M et al (2018) Does Parkinson’s disease start in the gut? Acta Neuropathol 135:1–12. https://doi.org/10.1007/s00401-017-1777-8
Vivacqua G, Latorre A, Suppa A et al (2016) Abnormal salivary total and oligomeric alpha-synuclein in Parkinson’s disease. PLoS One 11:e0151156. https://doi.org/10.1371/journal.pone.0151156
Kang W, Chen W, Yang Q et al (2016) Salivary total α-synuclein, oligomeric α-synuclein and SNCA variants in Parkinson’s disease patients. Sci Rep 6:28143. https://doi.org/10.1038/srep28143
Proulx M, De Courval FP, Wiseman MA, Panisset M (2005) Salivary production in Parkinson’s disease. Mov Disord 20:204–207. https://doi.org/10.1002/mds.20189
Lieverse AR (1999) Diet and the aetiology of dental calculus. Int J Osteoarchaeol 9:219–232. https://doi.org/10.1002/(sici)1099-1212(199907/08)9:4<219::aid-oa475>3.0.co;2-v
Radini A, Nikita E, Buckley S et al (2017) Beyond food: the multiple pathways for inclusion of materials into ancient dental calculus. Am J Phys Anthropol 162:71–83. https://doi.org/10.1002/ajpa.23147
Einarsdóttir ER, Gunnsteinsdóttir H, Hallsdóttir MH et al (2009) Dental health of patients with Parkinson’s disease in Iceland. Spec Care Dentist 29:123–127
Barbour R, Kling K, Anderson JP et al (2008) Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis 5:55–59
Oeckl P, Metzger F, Nagl M 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 Proteom 15:3126–3138. https://doi.org/10.1074/mcp.M116.059915
Eusebi P, Giannandrea D, Biscetti L et al (2017) Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 32:1389–1400. https://doi.org/10.1002/mds.27110
Shellis RP, Addy M (2014) The interactions between attrition, abrasion and erosion in tooth wear. In: Monographs in oral science, pp 32–45
Uversky VN, Li J, Fink AL (2001) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson’s disease and heavy metal exposure. J Biol Chem 276:44284–44296. https://doi.org/10.1074/jbc.M105343200
Acknowledgements
We thank all patients for their participation in this study and Stephen Meier for skilful technical assistance. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that they have no conflict of interest.
Ethical statement
All patients or their next of kin provided written informed consent to participate in the study. The study was conducted at the University of Ulm in compliance with university ethics guideline as well as German federal and state law.
Rights and permissions
About this article
Cite this article
Schmid, S., Goldberg-Bockhorn, E., Schwarz, S. et al. Alpha-synuclein is present in dental calculus but not altered in Parkinson’s disease patients in comparison to controls. J Neurol 265, 1334–1337 (2018). https://doi.org/10.1007/s00415-018-8847-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-018-8847-2