Objective/Rationale:
We have recently demonstrated that the nerves supplying the throat are directly affected in Parkinson’s disease (PD) by the same microscopic process that affects the brain, i.e. “Lewy-type synucleinopathy” (LTS). We hypothesize that swallowing difficulty in PD is primarily due to LTS in the nervous system of the upper part of the throat, larynx and upper esophagus. The objective of this project is two-fold: first, to document the presence and distribution of LTS in these regions, and to see if there is a relationship between LTS density and swallowing difficulty; second, to identify the exact site(s) that are most likely to have LTS, as these might be useful as a biopsy site to diagnose PD.
Project Description:
Autopsied upper throat, larynx and esophagus lining tissue obtained from 10 subjects with clinically diagnosed and neuropathologically confirmed PD and four age-matched normal controls without PD will be studied. The autopsy subjects were derived from the Arizona Study of Aging and Neurodegenerative Disease (AZSAND), a longitudinal clinicopathological study. All subjects received annual standardized neuropathological examinations. Standardized research neuro/movement examinations were performed by movement disorders specialists working with AZSAND and the Brain and Body Donation Program. In the PD group, there were five cases with swallowing difficulty and five cases without swallowing difficulty. For each case, six lining tissue samples (10x10 mm/each) will be obtained from the oropharynx (i.e., lateral posterior tongue, anterior tonsillar pillar, and oropharyngeal posterior wall), laryngopharynx (i.e., aryepiglottic fold and postcricoid region) and upper esophagus. The tissue will be sectioned and treated with special stains. The stained sections will be examined under a microscope to identify LTS.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This clinico-pathologic correlation study may provide a better understanding of the causes of swallowing difficulty in PD and therefore provide direction for therapeutic strategies. In addition, the results would be helpful for testing the feasibility of upper aerodigestive tract biopsy as a tissue-based diagnostic test for PD.
Anticipated Outcome:
The proposed work could document whether LTS can be identified in the PD throat and adjacent regions and which sampling site(s) have the greatest density of LTS. We expect that the density of LTS in these regions is greater in PD subjects with swallowing difficulty versus those without swallowing difficulty. This study will provide an initial documentation as to how much of the swallowing difficulty is accounted for by such pathology.