Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in parkinson disease

Liancai Mu, Stanislaw Sobotka, Jingming Chen, Hungxi Su, Ira Sanders, Charles Howard Adler, Holly A. Shill, John Nathaniel Caviness, Johan E. Samanta, Thomas G. Beach

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Parkinson disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor manifestations and CNS pathology. Current drug therapies can often stabilize these cardinal motor symptoms, and attention has shifted to the other motor and nonmotor symptoms of PD that are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug-resistant symptom because it leads to aspiration and pneumonia, the leading cause of death. Here, we present direct evidence for degeneration of the pharyngeal motor nerves in PD. We examined the cervical vagal nerve (cranial nerve X), pharyngeal branch of nerve X, and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, that is, from 10 patients with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. Alpha-synuclein aggregates were revealed in nerve X and the pharyngeal branch of nerve X, and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all of the PD patients but in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathologic process of PD. Notably, PD patients who have had dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves than those without dysphagia. These findings indicate that motor involvement of the pharynx in PD is one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number2
DOIs
StatePublished - Feb 2013

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Pharyngeal Muscles
alpha-Synuclein
Peripheral Nerves
Parkinson Disease
Pathology
Vagus Nerve
Deglutition Disorders
Synucleins
Pharynx
Aspiration Pneumonia
Drug Therapy
Neuromuscular Junction
Presynaptic Terminals
Pathologic Processes
Neurodegenerative Diseases
Nervous System
Cause of Death

Keywords

  • Alpha-synuclein aggregates
  • Dysphagia
  • Intramuscular nerve twigs
  • Lewy bodies
  • Lewy neurites
  • Motor nerve
  • Parkinson disease
  • Pharyngeal constrictor muscles
  • Pharyngeal plexus
  • Upper esophageal sphincter
  • Vagus nerve.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in parkinson disease. / Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles Howard; Shill, Holly A.; Caviness, John Nathaniel; Samanta, Johan E.; Beach, Thomas G.

In: Journal of Neuropathology and Experimental Neurology, Vol. 72, No. 2, 02.2013, p. 119-129.

Research output: Contribution to journalArticle

Mu, Liancai ; Sobotka, Stanislaw ; Chen, Jingming ; Su, Hungxi ; Sanders, Ira ; Adler, Charles Howard ; Shill, Holly A. ; Caviness, John Nathaniel ; Samanta, Johan E. ; Beach, Thomas G. / Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in parkinson disease. In: Journal of Neuropathology and Experimental Neurology. 2013 ; Vol. 72, No. 2. pp. 119-129.
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AU - Sanders, Ira

AU - Adler, Charles Howard

AU - Shill, Holly A.

AU - Caviness, John Nathaniel

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AU - Beach, Thomas G.

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AB - Parkinson disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor manifestations and CNS pathology. Current drug therapies can often stabilize these cardinal motor symptoms, and attention has shifted to the other motor and nonmotor symptoms of PD that are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug-resistant symptom because it leads to aspiration and pneumonia, the leading cause of death. Here, we present direct evidence for degeneration of the pharyngeal motor nerves in PD. We examined the cervical vagal nerve (cranial nerve X), pharyngeal branch of nerve X, and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, that is, from 10 patients with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. Alpha-synuclein aggregates were revealed in nerve X and the pharyngeal branch of nerve X, and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all of the PD patients but in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathologic process of PD. Notably, PD patients who have had dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves than those without dysphagia. These findings indicate that motor involvement of the pharynx in PD is one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.

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