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Diminished tyrosine hydroxylase immunoreactivity in the cardiac conduction system and myocardium in Parkinson’s disease: an anatomical study

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Abstract

Clinical and autopsy studies have consistently reported cardiac sympathetic dysfunction in the left ventricular wall in patients with Parkinson’s disease (PD). Whether the nerve fibers of the cardiac conduction system or the atrial walls are equally affected in this disease process has not yet been well documented. Therefore, the aim of this study was to investigate sympathetic nerves in the cardiac conduction system as well as in the walls of all four heart chambers in patients with PD, in incidental Lewy body disease (iLBD), and in controls. Heart tissue from five PD patients, two iLBD cases, and seven controls were investigated immunohistochemically using antibodies directed against tyrosine hydroxylase (TH) and α-synuclein (syn-1). A marked diminution of TH immunoreactivity (IR) within nerve fibers was observed in four PD patients and in both individuals with iLBD. In contrast, all control subjects displayed dense TH-IR nerve structures. The depletion in TH-IR involved not only the ventricles, but also the conduction system and the atrium showing a global change within cardiac TH-IR nerve fibers in the course of PD. In conclusion, the alterations in cardiac sympathetic nerves of patients with PD or in individuals with iLBD are homogeneous and global within the heart. The clinical implications related to this complete cardiac sympathetic dysfunction, including clinical correlates, diagnostic implications, and treatment, however, remain to be determined in a larger autopsy-controlled cohort of prospectively followed individuals.

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Acknowledgments

This study was funded by the Michael J. Fox Foundation for Parkinson’s Research (New York City, USA). The authors wish to thank Prof. Martin-Leo Hansmann, Director of the Dr. Senckenberg Institute for Pathology, Goethe University Frankfurt am Main, and Dr. Susanne Braun, Chief Pathologist, Offenbach Clinic, for providing autopsy material. They are also grateful to Mr. Mohamed Bouzrou (Goethe University Frankfurt) and Ms. Gabriele Ehmke (University of Ulm) for immunostaining, Ms. Inge Szász-Jacobi, who assisted with the graphics, and the Braak Collection (Goethe University Frankfurt).

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  1. Estifanos Ghebremedhin

    Present address: Anatomy and Developmental Biology, School of Biomedical Sciences, University of Queensland, St Lucia, QLD, 4072, Australia

Authors and Affiliations

  1. Institute of Clinical Neuroanatomy, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany

    Estifanos Ghebremedhin

  2. Laboratory of Neuropathology, Center for Clinical Research, University of Ulm, 89081, Ulm, Germany

    Estifanos Ghebremedhin

  3. Clinical Neuroanatomy, Department of Neurology, Center for Clinical Research, University of Ulm, 89081, Ulm, Germany

    Kelly Del Tredici & Heiko Braak

  4. The Parkinson’s Institute, Sunnyvale, CA, USA

    James W. Langston

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  1. Estifanos Ghebremedhin
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  2. Kelly Del Tredici
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  3. James W. Langston
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  4. Heiko Braak
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Correspondence to Estifanos Ghebremedhin.

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Ghebremedhin, E., Del Tredici, K., Langston, J.W. et al. Diminished tyrosine hydroxylase immunoreactivity in the cardiac conduction system and myocardium in Parkinson’s disease: an anatomical study. Acta Neuropathol 118, 777–784 (2009). https://doi.org/10.1007/s00401-009-0596-y

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  • DOI: https://doi.org/10.1007/s00401-009-0596-y

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