Funded Studies
Objective/Rationale:
The heart, particularly the conduction system, is influenced by the parasympathetic and sympathetic nervous systems. Recently, early-occurring Parkinson’s disease-related Lewy pathology was reported in sympathetic nerves. What is unknown, however, is whether the parasympathetic innervation also becomes involved in Parkinson’s disease and how the development of cardiac pathology fits into the neuropathological staging system for the brain published by our Frankfurt group in 2003. This study of cardiac Lewy pathology will run parallel to electrophysiologic studies carried out by the Parkinson’s Institute in Sunnyvale under the direction of J. William Langston, MD. The second half of the project is a pilot study and is designed to determine the pathoanatomical correlates of dementia in sporadic Parkinson’s disease. The pilot study requires neuropathological examination and staging of full-size brain hemisphere sections and brainstem serial sections from 27 individuals with clinical evidence of dementia who had met recognized diagnostic criteria for Parkinson’s disease.
Project Description:
Both project components entail dissection and detailed light microscopic study of autopsy material (whole brains and portions of the epicard, myocard, conduction system, and endocard). Immunocytochemistry will be used on unconventionally thick (100 micrometer) tissue sections, a technique originally developed by the PI especially to meet the demands of studying the brain and large portions of the human nervous system.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The results of the first part of the project could help to provide a badly needed noninvasive biomarker for early Parkinson’s disease. The findings gained from the pilot study can be used to establish clinicopathological correlations of mild cognitive impairment and dementia in individuals with Parkinson’s disease.
Anticipated Outcome:
This study aims to provide new insights into the progression of Parkinson’s disease by placing the development of the Lewy pathology in the heart within the framework of what is already known about disease progression within the central nervous system (brain). The staging system proposed by our group for the brain can be extended to include peripheral lesions in cardiac innervation.
Progress Report
Drs Braak and Del Tredici continue to make fundamental discoveries regarding the extent of pathology of PD especially outside of the central nervous system. To date, they have described pathological changes in the nerves innervating the heart and in the cardiac conduction system that may indicate early changes associated with Parkinson's disease. Additionally, synuclein pathology was found in the submandibular gland and anatomically related structures in Parkinson's patients as well as in incidental Lewy body disease - a hypothesis-generating finding that could lead to new ways to develop biomarkers.