Alpha-synuclein in salivary gland as biomarker for Parkinson’s disease
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Flaminia Campo
, Raffaella Carletti
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.
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.
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, 858–864.10.1212/WNL.0000000000000204Suche in 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, 250–256.10.1002/mds.26476Suche in Google Scholar PubMed
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, 130–136.10.1097/NEN.0b013e3182805c72Suche in Google Scholar
Bennett, M.C. (2005). The role of α-synuclein in neurodegenerative diseases. Pharmacol. Ther. 5, 311–331.10.1016/j.pharmthera.2004.10.010Suche in 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, 87–96.10.1046/j.1471-4159.2001.00021.xSuche in Google Scholar PubMed
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, 99–101.10.1016/j.parkreldis.2017.02.031Suche in 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, 188–190.10.1002/mds.23344Suche in Google Scholar PubMed
de Lau, L.M. and Breteler, M.M. (2006). Epidemiology of Parkinson’s disease. Lancet Neurol. 5, 525–535.10.1016/S1474-4422(06)70471-9Suche in Google Scholar PubMed
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, 703–713.10.1007/s00401-010-0665-2Suche in Google Scholar PubMed
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, 1150–1157.10.1016/S1474-4422(09)70238-8Suche in Google Scholar PubMed
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, 62–64.10.1016/j.neulet.2013.07.016Suche in Google Scholar PubMed
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, 1575–1580.10.1007/s10072-015-2190-5Suche in Google Scholar PubMed
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, 181–184.10.1136/jnnp.55.3.181Suche in Google Scholar PubMed
Hughes, A.J., Daniel, S.E., and Lees, A.J. (2001). Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology 57, 1497–1499.10.1212/WNL.57.8.1497Suche in Google Scholar PubMed
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, 74–81.10.1016/S0194-5998(98)70378-XSuche in Google Scholar PubMed
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, 467–475.10.1016/0896-6273(95)90302-XSuche in Google Scholar PubMed
Jean, A. (1984). Control of the central swallowing program by inputs from the peripheral receptors. J. Autonomic Nervous Syst. 10, 225–233.10.1016/0165-1838(84)90017-1Suche in 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, 1670–1676.10.1002/mds.23720Suche in Google Scholar PubMed
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, 501–503.10.1038/nm1746Suche in Google Scholar PubMed
Marshall, J.F. (1979). Somatosensory inattention after dopamine-depleting intracerebral 6-OHDA injections: spontaneous recovery and pharmacological control. Brain Res. 177, 311–324.10.1016/0006-8993(79)90782-0Suche in Google Scholar PubMed
Mochizuki, H., Choong, C.J., and Masliah, E. (2018). A refined concept: α-synuclein dysregulation disease. Neurochem. Int. 119, 84–96.10.1016/j.neuint.2017.12.011Suche in Google Scholar PubMed
Mukherjee, A., Biswas, A., and Das, S.K. (2016). Gut dysfunction in Parkinson’s disease. World J. Gastroenterol. 22, 5742–5752.10.3748/wjg.v22.i25.5742Suche in Google Scholar PubMed PubMed Central
Müller, T., Palluch, R., and Jackowski, J. (2011). Caries and periodontal disease in patients with Parkinson’s disease. Spec. Care Dentist. 31, 178–181.10.1111/j.1754-4505.2011.00205.xSuche in Google Scholar PubMed
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, 42–49.10.1590/S0004-28032013000100009Suche in Google Scholar PubMed
Proulx, M., de Courval, F.P., Wiseman, M.A., and Panisset, M. (2005). Salivary production in Parkinson’s disease. Mov. Disord. 20, 204–207.10.1002/mds.20189Suche in Google Scholar PubMed
Rajput, A.H., Rozdilsky, B., and Rajput, A. (1991). Accuracy of clinical diagnosis in Parkinsonism – a prospective study. Can. J. Neurol. Sci. 18, 275–278.10.1017/S0317167100031814Suche in Google Scholar PubMed
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, 247–261.10.1111/ene.12753Suche in Google Scholar PubMed
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, 16–27.10.1111/j.1749-6632.2000.tb06900.xSuche in Google Scholar PubMed
Srivanitchapoom, P., Pandey, S., and Hallett, M. (2014). Drooling in Parkinson’s disease: a review. Parkinsonism Relat. Disord. 20, 1109–1118.10.1016/j.parkreldis.2014.08.013Suche in Google Scholar PubMed PubMed Central
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, 11282–11286.10.1073/pnas.90.23.11282Suche in Google Scholar PubMed PubMed Central
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, 708–718.10.1016/S1474-4422(16)00080-6Suche in Google Scholar PubMed
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, 359–368.10.2217/bmm-2016-0366Suche in Google Scholar PubMed
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, 13709–13715.10.1021/bi961799nSuche in Google Scholar PubMed
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, 19509–19512.10.1074/jbc.274.28.19509Suche in Google Scholar PubMed
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, 379482.10.1155/2015/379482Suche in Google Scholar PubMed PubMed Central
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Artikel in diesem Heft
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Artikel in diesem Heft
- Frontmatter
- Alpha-synuclein in salivary gland as biomarker for Parkinson’s disease
- Determining the early corticospinal-motoneuronal responses to strength training: a systematic review and meta-analysis
- The role of neurovascular unit damage in the occurrence and development of Alzheimer’s disease
- Functions of adiponectin signaling in regulating neural plasticity and its application as the therapeutic target to neurological and psychiatric diseases
- A review of the use of EEG connectivity to measure the neurological characteristics of the sensory features in young people with autism
- Multiple sclerosis – the remarkable story of a baffling disease
- Melatonin and its anti-glioma functions: a comprehensive review
- The role of fibroblast growth factors and their receptors in gliomas: the mutations involved
- Application of quercetin in neurological disorders: from nutrition to nanomedicine