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Reviews in the Neurosciences

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Alpha-synuclein in salivary gland as biomarker for Parkinson’s disease

Flaminia Campo
  • Corresponding author
  • Dipartimento di Organi di Senso, “Sapienza” Università di Roma, Viale del Policlinico 155, I-00161 Rome, Italy
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/ Raffaella Carletti
  • Dipartimento di Scienze Radiologiche, Oncologiche e Anatomopatologiche, “Sapienza” Università di Roma, Viale Regina Elena 324, I-00161 Rome, Italy
  • Other articles by this author:
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/ Massimo Fusconi
  • Dipartimento di Organi di Senso, “Sapienza” Università di Roma, Viale del Policlinico 155, I-00161 Rome, Italy
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/ Clelia Pellicano
  • Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso, “Sapienza” Università di Roma, Via di Grottarossa 1035, I-00189 Rome, Italy
  • IRCCS “Fondazione Santa Lucia”, Via Ardeatina 306, I-00179 Rome, Italy
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/ Francesco E. Pontieri
  • Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso, “Sapienza” Università di Roma, Via di Grottarossa 1035, I-00189 Rome, Italy
  • IRCCS “Fondazione Santa Lucia”, Via Ardeatina 306, I-00179 Rome, Italy
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/ Cira R. Di Gioia
  • Dipartimento di Scienze Radiologiche, Oncologiche e Anatomopatologiche, “Sapienza” Università di Roma, Viale Regina Elena 324, I-00161 Rome, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Marco de Vincentiis
  • Dipartimento di Organi di Senso, “Sapienza” Università di Roma, Viale del Policlinico 155, I-00161 Rome, Italy
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Published Online: 2018-11-24 | DOI: https://doi.org/10.1515/revneuro-2018-0064

Abstract

Estimates of the accuracy of clinical diagnosis of Parkinson’s disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: ‘salivary gland biopsy for PD’, ‘PD and dysphagia’, ‘alpha-synuclein and salivary gland’. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

Keywords: biomarker; dysphagia; Parkinson’s disease; phosphorylated-α-synuclein; salivary gland biopsy; α-synuclein

References

  • Adler, C.H., Dugger, B.N., Hinni, M.L., Lott, D.G., Driver-Dunckley, E., Hidalgo, J., Henry-Watson, J., Serrano, G., Sue, L.I., Nagel, T., et al. (2014). Submandibular gland needle biopsy for the diagnosis of Parkinson disease. Neurology 82, 858–864.Google Scholar

  • Adler, C.H., Dugger, B.N., Hentz, J.G., Hinni, M.L., Lott, D.G., Driver-Dunckley, E., Mehta, S., Serrano, G., Sue, L.I., Duffy, A., et al. (2016). Peripheral synucleinopathy in early Parkinson’s disease: submandibular gland needle biopsy findings. Mov. Disord. 31, 250–256.Google Scholar

  • Beach, T.G., Adler, C.H., Dugger, B.N., Serrano, G., Hidalgo, J., Henry-Watson, J., Shill, H.A., Sue, L.I., Sabbagh, M.N., Akiyama, H., et al. (2013). Submandibular gland biopsy for the diagnosis of Parkinson disease. J. Neuropathol. Exp. Neurol. 72, 130–136.Google Scholar

  • Bennett, M.C. (2005). The role of α-synuclein in neurodegenerative diseases. Pharmacol. Ther. 5, 311–331.Google Scholar

  • Campbell, B.C., McLean, C.A., Culvenor, J.G., Gai, W.P., Blumbergs, P.C., Jäkälä, P., Beyreuther, K., Masters, C.L., and Li, Q.X. (2001). The solubility of α-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. J. Neurochem. 76, 87–96.Google Scholar

  • Carletti, R., Campo, F., Fusconi, M., Pellicano, C., De Vincentiis, M., Pontieri, F.E., and Di Gioia, C.R. (2018). Phosphorylated α-synuclein immunoreactivity in nerve fibers from minor salivary glands in Parkinson’s disease. Parkinsonism Relat. Disord. 38, 99–101.Google Scholar

  • Cersósimo, M.G., Perandones, C., Micheli, F.E., Raina, G.B., Beron, A.M., Nasswetter, G., Radrizzani, M., and Benarroch E.E. (2011). Alpha-synuclein immunoreactivity in minor salivary gland biopsies of Parkinson’s disease patients. Mov. Disord. 26, 188–190.Google Scholar

  • de Lau, L.M. and Breteler, M.M. (2006). Epidemiology of Parkinson’s disease. Lancet Neurol. 5, 525–535.Google Scholar

  • Del Tredici, K., Hawkes, C.H., Ghebremedhin, E., and 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.Google Scholar

  • Dickson, D.W., Braak, H., Duda, J.E., Duyckaerts, C., Gasser, T., Halliday, G.M., Hardy, J., Leverenz, J.B., Del Tredici, K., Wszolek, Z.K., et al. (2009). Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol. 8, 1150–1157.Google Scholar

  • Folgoas, E., Lebouvier, T., Leclair-Visonneau, L., Cersosimo, M.G., Barthelaix, A., Derkinderen, P., and Letournel, F. (2013). Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology. Neurosci. Lett. 551, 62–64.Google Scholar

  • Gao, L., Chen, H., Li, X., Li, F., Ou-Yang, Q., and Feng, T. (2015). The diagnostic value of minor salivary gland biopsy in clinically diagnosed patients with Parkinson’s disease: comparison with DAT Pet scans. Neurol. Sci. 36, 1575–1580.Google Scholar

  • Hughes, A.J., Daniel, S.E., Kilford, L., and Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55, 181–184.Google Scholar

  • Hughes, A.J., Daniel, S.E., and Lees, A.J. (2001). Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology 57, 1497–1499.Google Scholar

  • Inagi, K., Schultz, E., and Ford, C.N. (1998). An anatomic study of the rat larynx: establishing the rat model for neuromuscular function. Otolaryngol. Head Neck Surg. 118, 74–81.Google Scholar

  • Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., de Silva, H.A., Kittel, A., and Saitoh T. (1995). The precursor protein of non-A β component of Alzheimer’s disease amyloid is a presynapticprotein of the central nervous system. Neuron 14, 467–475.Google Scholar

  • Jean, A. (1984). Control of the central swallowing program by inputs from the peripheral receptors. J. Autonomic Nervous Syst. 10, 225–233.Google Scholar

  • Kalf, J.G., Munneke, M., van den Engel-Hoek, L., de Swart, B.J., Borm, G.F., Bloem, B.R., and Zwarts, M.J. (2011). Pathophysiology of diurnal drooling in Parkinson’s disease. Mov. Disord. 26, 1670–1676.Google Scholar

  • Li, J.Y., Englund, E., Holton, J.L., Soulet, D., Hagell, P., Lees, A.J., Lashley, T., Quinn, N.P., Rehncrona, S., Björklund, A., et al. (2008). Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat. Med. 14, 501–503.Google Scholar

  • Marshall, J.F. (1979). Somatosensory inattention after dopamine-depleting intracerebral 6-OHDA injections: spontaneous recovery and pharmacological control. Brain Res. 177, 311–324.Google Scholar

  • Mochizuki, H., Choong, C.J., and Masliah, E. (2018). A refined concept: α-synuclein dysregulation disease. Neurochem. Int. 119, 84–96.Google Scholar

  • Mukherjee, A., Biswas, A., and Das, S.K. (2016). Gut dysfunction in Parkinson’s disease. World J. Gastroenterol. 22, 5742–5752.Google Scholar

  • Müller, T., Palluch, R., and Jackowski, J. (2011). Caries and periodontal disease in patients with Parkinson’s disease. Spec. Care Dentist. 31, 178–181.Google Scholar

  • Nicaretta, D.H., Rosso, A.L., Mattos, J.P., Maliska, C., and Costa, M.M. (2013). Dysphagia and sialorrhea: the relationship to Parkinson’s disease. Arq. Gastroenterol. 50, 42–49.Google Scholar

  • Proulx, M., de Courval, F.P., Wiseman, M.A., and Panisset, M. (2005). Salivary production in Parkinson’s disease. Mov. Disord. 20, 204–207.Google Scholar

  • Rajput, A.H., Rozdilsky, B., and Rajput, A. (1991). Accuracy of clinical diagnosis in Parkinsonism – a prospective study. Can. J. Neurol. Sci. 18, 275–278.Google Scholar

  • Schneider, S.A., Boettner, M., Alexoudi, A., Zorenkov, D., Deuschl, G., and Wedel, T. (2016). Can we use peripheral tissue biopsies to diagnose Parkinson’s disease? A review of the literature. Eur. J. Neurol. 23, 247–261.Google Scholar

  • Spillantini, M.G. and Goedert, M. (2000). The α-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann. NY Acad. Sci. 920, 16–27.Google Scholar

  • Srivanitchapoom, P., Pandey, S., and Hallett, M. (2014). Drooling in Parkinson’s disease: a review. Parkinsonism Relat. Disord. 20, 1109–1118.Google Scholar

  • Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D.A., Kondo, J., Ihara, Y., and Saitoh, T. (1993). Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimerdisease. Proc. Natl. Acad. Sci. USA 90, 11282–11286.Google Scholar

  • Vilas, D., Iranzo, A., Tolosa, E., Aldecoa, I., Berenguer, J., Vilaseca, I., Martí, C., Serradell, M., Lomeña, F., Alós, L., et al. (2016). Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye movement sleep behaviour disorder: a case-control study. Lancet Neurol. 15, 708–718.Google Scholar

  • Visanji, N.P., Mollenhauer, B., Beach, T.G., Adler, C.H., Coffey, C.S., Kopil, C.M., Dave, K.D., Foroud, T., Chahine, L., and Jennings, D. (2017). Systemic synuclein sampling study (S4). The systemic synuclein sampling study: toward a biomarker for Parkinson’s disease. Biomark. Med. 11, 359–368.Google Scholar

  • Weinreb, P.H., Zhen, W., Poon, A.W., Conway, K.A., and Lansbury, P.T. Jr. (1996). NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35, 13709–13715.Google Scholar

  • Wood, S.J., Wypych, J., Steavenson, S., Louis, J.C., Citron, M., and Biere, A.L. (1999). α-Synuclein fibrillogenesis is nucleation dependent. Implications for the pathogenesis of Parkinson’s disease. J. Biol. Chem. 274, 19509–19512.Google Scholar

  • Zlotnik, Y., Balash, Y., Korczyn, A.D., Giladi, N., and Gurevich, T. (2015). Disorders of the oral cavity in Parkinson’s disease and parkinsonian syndromes. Parkinsons Dis. 2015, 379482.Google Scholar

About the article

Received: 2018-06-22

Accepted: 2018-08-10

Published Online: 2018-11-24


Funding: This study was not funded.

Conflict of interest statement: The authors have no conflict of interest. There are not financial or personal relationships with other people or organizations that could inappropriately influence the authors’ actions.

Ethical approval: This article does not contain any studies with animals performed by any of the authors.


Citation Information: Reviews in the Neurosciences, 20180064, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2018-0064.

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