25-07-08(21:56:05)
Authors:
Europe: Li J-Y 1, Englund E 2, Holton JL 3, Soulet D 1, Hagell P 4, Lees AJ 3, Lashley T 3, Quinn NP 5, Rehncrona S 6, Bjoörklund A 7, Widner H 4, Revesz T 3,9, Lindvall O 4,8,9 and Brundin P 1, 9
USA: Kordower JH 1, Chu Y 1, Hauser RA 2, Freeman TB 3 and Olanow CW 4
Institutions:
Europe:
1 Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, 221 84 Lund, Sweden.
2 Division of Neuropathology, Lund University Hospital, 221 85 Lund, Sweden.
3 Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
4 Division of Neurology, Lund University Hospital, 221 85 Lund, Sweden.
5 Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
6 Division of Neurosurgery, Lund University Hospital, 221 85 Lund, Sweden.
7 Neurobiology Unit and 8 Section of Restorative Neurology, Wallenberg Neuroscience Center, 221 84 Lund, Sweden.
9 These authors are senior authors.
USA:
1 Department of Neurological Sciences and Center for Brain Repair, Rush University Medical Center, 1735 West Harrison Street, Chicago, Illinois 60612, USA.
Departments of 2 Neurology and 3 Neurosurgery, University of South Florida, 2 Columbia Drive, Tampa, Florida 33606, USA.
4 Department of Neurology, 1 Annenberg Plaza, Mount Sinai School of Medicine, New York, NY 10029, USA.
Title of abstract : Long-term surviving transplanted dopamine neurons exhibit α-synuclein accumulation and Lewy bodies in Parkinson patients
Abstract text:
Cell replacement therapy with fetal ventral mesencephalic tissues has been documented to be beneficial in some open-labeled trials. F-dopa and raclopride PET imaging has shown functional grafts at least ten years after transplantation. Here, we report postmortem studies of Parkinson patients who were parts of one European and one North American trial. One European case received bilateral intrastriatal transplants 12 years and 16 years before death, the other was implanted 11 and 13 years prior to dying. One North American case received bilateral grafts into putamen 14 years before death. We observed that substantial numbers of transplanted dopamine neurons, immunopositive for TH and VMAT2 (but not DAT), survived more than a decade after surgery. Remarkably, we observed that grafted neurons exhibited cytoplasmic α-synuclein-immunoreactivity in cell bodies, as well as typical Lewy bodies and Lewy neurites in the patients who had lived for 11-16 years after grafting. We validated the presence of Lewy bodies by thioflavin S staining. The changes in aggregated and non-aggregated α-synuclein were age-dependent. In the European case, less than 2% of grafted cells containing neuromelanin displayed typical α-synuclein-positive Lewy bodies in the 12 year-old graft while the proportion exceeded 5% in the 16 year-old graft. Our studies suggest that the host microenvironment has a negative impact on the neurons grafted ectopically to the striatum and the disease-processes are propagated from host to the implanted cells. These observations have important implications for our understanding of PD pathogenesis.
