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Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease

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Abstract

Lewy bodies, the histologic hallmark of Parkinson’s disease (PD), are detected in the brains of about 10% of clinically normal people over the age of 60 years. When Lewy bodies are found in normal individuals, the process is sometimes referred to as incidental Lewy body disease (iLBD). The distribution of Lewy bodies in iLBD is similar to the distribution in PD, but neuronal populations vulnerable to Lewy bodies do not show significant neuronal loss in iLBD. It remains unknown if Lewy bodies in this setting represent pre-symptomatic PD or an age-related change unrelated to PD. To address this question we identified cases of iLBD and used a marker for dopaminergic and noradrenergic neurons, tyrosine hydroxylase (TH), to determine if there were changes similar to those found in PD. TH immunoreactivity in the striatum and the epicardial nerve fibers was decreased in iLBD compared to normal controls, but not to the same extent as in PD. The findings suggest that iLBD is preclinical PD and that the lack of symptoms is due to subthreshold pathology.

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Acknowledgments

This study is supported by the Morris K. Udall Center for Excellence in Parkinson’s Disease Research at Mayo Clinic (NIH P50-NS40256-09). The authors acknowledge Michael Oelkers and Allison Kendall for their efforts in acquiring tissue for these studies through the Mayo Tissue Registry. The assistance of Virginia Phillips, Linda Rousseau and Monica Casey-Castanedes for histologic and immunohistochemistry studies is also greatly appreciated.

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Authors and Affiliations

  1. Neuropathology Laboratory, Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Dennis W. Dickson, Hiroshige Fujishiro, Anthony DelleDonne, Joshua Menke & Zeshan Ahmed

  2. Neurological Associates of Tulsa, Tulsa, OK, USA

    Kevin J. Klos

  3. Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Joseph E. Parisi

  4. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Keith A. Josephs, Roberta Frigerio, Melinda Burnett & J. Eric Ahlskog

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  1. Dennis W. Dickson
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  2. Hiroshige Fujishiro
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  3. Anthony DelleDonne
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  4. Joshua Menke
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  5. Zeshan Ahmed
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  6. Kevin J. Klos
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  7. Keith A. Josephs
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  8. Roberta Frigerio
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  9. Melinda Burnett
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  10. Joseph E. Parisi
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  11. J. Eric Ahlskog
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Correspondence to Dennis W. Dickson.

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Dickson, D.W., Fujishiro, H., DelleDonne, A. et al. Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease. Acta Neuropathol 115, 437–444 (2008). https://doi.org/10.1007/s00401-008-0345-7

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  • DOI: https://doi.org/10.1007/s00401-008-0345-7

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