Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation

Nature Medicine volume 14, pages501–503(2008)Cite this article

Abstract

Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11–16 years) developed α-synuclein–positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.

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Figure 1: Surviving dopaminergic neurons labeled with antibody to tyrosine hydroxylase in a graft transplanted 16 years before death in subject 3.
Figure 2: α-synuclein–positive Lewy bodies in host substantia nigra and grafted dopaminergic neurons in subject 3 (a–d) and subject 8 (e).

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Acknowledgements

This work was supported by grants from the Swedish Research Council, Swedish Parkinson Foundation, the Nordic Center of Excellence on Neurodegeneration and The Strong Research Environment of the Swedish Research Council (NeuroFortis). The Queen Square Brain Bank is supported by the Reta Lila Weston Institute of Neurological Studies and the Progressive Supranuclear Palsy (Europe) Association. T.R. and J.L.H. are supported by grants from the Parkinson's Disease Society, UK, the Alzheimer's Research Trust and the Sarah Matheson Trust. The authors wish to thank B.-M. Lindberg and A. Persson for their excellent technical support. E.E. and J.L.H. contributed equally as the second authors.

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Author notes

  1. Tamas Revesz, Olle Lindvall and Patrik Brundin: These authors are senior authors.

Affiliations

  1. Department of Experimental Medical Science, Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund, 221 84, Sweden

    Jia-Yi Li, Denis Soulet & Patrik Brundin

  2. Division of Neuropathology, Lund University Hospital, Lund, 221 85, Sweden

    Elisabet Englund

  3. Department of Molecular Neuroscience, Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

    Janice L Holton, Andrew J Lees, Tammaryn Lashley & Tamas Revesz

  4. Division of Neurology, Lund University Hospital, Lund, 221 85, Sweden

    Peter Hagell, Håkan Widner & Olle Lindvall

  5. Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

    Niall P Quinn

  6. Division of Neurosurgery, Lund University Hospital, Lund, 221 85, Sweden

    Stig Rehncrona

  7. Neurobiology Unit, Lund, 221 84, Sweden

    Anders Björklund

  8. Section of Restorative Neurology, Wallenberg Neuroscience Center, Lund, 221 84, Sweden

    Olle Lindvall

Authors
  1. Jia-Yi Li
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  2. Elisabet Englund
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  12. Tamas Revesz
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  14. Patrik Brundin
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Contributions

J.-Y.L. designed and performed the detailed morphological analysis of most of the material from subject 3. E.E. and J.L.H. did autopsy and routine neuropathology of subjects 3 and 8, respectively. J.L.H. and T.R. designed and T.L. performed the detailed morphological analysis of subject 8. A.B. provided expertise in neural transplantation. D.S. provided expertise regarding graft reconstruction, imaging and microglia staining and also generated figures. P.H. assisted in the care of subject 3 and provided data related to clinical follow-up. H.W. and N.P.Q. took care of subjects 3 and 8, respectively. A.J.L. provided clinical evaluation for subject 8. S.R. operated on both subjects. P.B. dissected and prepared tissue for both surgeries and participated in the morphological assessment of subject 3. O.L. took care of subject 3 and headed the clinical transplantation program. J.-Y.L., J.L.H., T.R., O.L. and P.B. wrote the manuscript. All authors gave input to the manuscript.

Corresponding author

Correspondence to Patrik Brundin.

Supplementary information

Supplementary Text and Figures

Supplementary Figs. 1–4 and Supplementary Methods (PDF 1832 kb)

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Li, J., Englund, E., Holton, J. et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14, 501–503 (2008). https://doi.org/10.1038/nm1746

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