Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients

Liancai Mu, Jingming Chen, Stanislaw Sobotka, Themba Nyirenda, Brian Benson, Fiona Gupta, Ira Sanders, Charles H. Adler, John N. Caviness, Holly A. Shill, Marwan Sabbagh, Johan E. Samanta, Lucia I. Sue, Thomas G. Beach

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue–pharynx–larynx–upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Original languageEnglish (US)
Pages (from-to)404-417
Number of pages14
JournalDysphagia
Volume30
Issue number4
DOIs
StatePublished - Aug 26 2015

Keywords

  • Alpha-synuclein histopathology
  • Dysphagia
  • Lewy-type synucleinopathy
  • Parkinson’s disease
  • Peripheral sensory nerves
  • Upper aerodigestive tract

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Gastroenterology
  • Speech and Hearing

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    Mu, L., Chen, J., Sobotka, S., Nyirenda, T., Benson, B., Gupta, F., Sanders, I., Adler, C. H., Caviness, J. N., Shill, H. A., Sabbagh, M., Samanta, J. E., Sue, L. I., & Beach, T. G. (2015). Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients. Dysphagia, 30(4), 404-417. https://doi.org/10.1007/s00455-015-9612-7