Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease

Authors

  • Anke A. Dijkstra MSc,

    Corresponding author
    1. Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands
    • Correspondence to: Anke A. Dijkstra, Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: a.dijkstra@vumc.nl

    Search for more papers by this author
  • Pieter Voorn PhD,

    1. Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands
    Search for more papers by this author
  • Henk W. Berendse MD, PhD,

    1. Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands
    Search for more papers by this author
  • Henk J. Groenewegen MD, PhD,

    1. Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands
    2. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
    Search for more papers by this author
  • Netherlands Brain Bank,

    1. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
    Search for more papers by this author
  • Annemieke J.M. Rozemuller MD, PhD,

    1. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
    2. Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
    Search for more papers by this author
  • Wilma D.J. van de Berg PhD

    1. Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands
    Search for more papers by this author

  • Funding agencies: This study was supported by the Stichting Internationaal Parkinson Fonds (IPF; The Netherlands) and Prinses Beatrix Spierfonds (The Netherlands).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

To gain a better understanding of the significance of α-synuclein pathological conditions during disease progression in Parkinson's disease, we investigated whether 1) nigral neuronal loss in incidental Lewy body disease and Parkinson's disease donors is associated with the local burden α-synuclein pathological conditions during progression of pathological conditions; 2) the burden and distribution of α-synuclein pathological conditions are related to clinical measures of disease progression. Post-mortem tissue and medical records of 24 Parkinson's disease patients, 20 incidental Lewy body disease donors, and 12 age-matched controls were obtained from the Netherlands Brain Bank for morphometric analysis. We observed a 20% decrease in nigral neuronal cell density in incidental Lewy body disease compared with controls. Nigral neuronal loss (12%) was already observed before the appearance α-synuclein aggregates. The progression from Braak α-synuclein stage 3 to 4 was associated with a significant decline in neuronal cell density (46%). Nigral neuronal loss increased with later Braak α-synuclein stages but did not vary across consecutive Braak α-synuclein stages. We observed a negative correlation between neuronal density and local α-synuclein burden in the substantia nigra of Parkinson's disease patients (ρ = −0.54), but no relationship with Hoehn & Yahr stage or disease duration. In conclusion, our findings cast doubt on the pathogenic role of α-synuclein aggregates in elderly, but do suggest that the severity of neurodegeneration and local burden of α-synuclein pathological conditions are closely coupled during disease progression in Parkinson's disease. © 2014 International Parkinson and Movement Disorder Society

Ancillary