Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation
Abstract
Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-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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Previous evidence suggested prion-like cell-to-cell transmission of α-synuclein.
“Previous evidence suggested “prion-like” cell-to-cell transmission of α-synuclein9,10.”
From Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration (2020) · cites this paper as [10]
The most widely cited studies in support of the prion-like spread of LRP come from post-mortem studies of two PD patient cohorts who received robust long-term intrastriatal grafts of human fetal midbrain tissue.
“The most widely cited studies in support of the prion-like spread of LRP comes from post-mortem studies of two PD patient cohorts who received robust long-term intrastriatal grafts of human fetal midbrain tissue [205–208].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [205]
In post-mortem studies of PD patients with intrastriatal grafts, 1-5% of grafted dopaminergic neurons exhibited detectable LRP 12-22 years post-transplantation.
“These studies showed that 1-5% of the grafted dopaminergic neurons exhibited detectable LRP 12-22 years post-transplantation (n=2 patients [205], n=1 patient [206], n=3 patients [207]), which increased to 11-12% after 24 years (n=1 patient [208]).”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [205]
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Self-citation
- Authors
- Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., Widner, H., Revesz, T., Lindvall, O., & Brundin, P.
- Affiliations
- Skåne University Hospital (SE)
- National Hospital for Neurology and Neurosurgery (GB)
- Lund University (SE)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Brundin, Patrik
- ORCID
- Venue
- Nature Medicine
- Published
- 2008-04-06
- Volume
- 14
- Issue
- 5
- Pages
- 501-503
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2050647292
- Cited by
- 1,845
- References
- 17
- Citations by year
- 2026: 51 · 2025: 75 · 2024: 82 · 2023: 71 · 2022: 119 · 2021: 128 · 2020: 143 · 2019: 118 · 2018: 102 · 2017: 117 · 2016: 106 · 2015: 99 · 2014: 103 · 2013: 118 · 2012: 99
- FWCI
- 65.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Parkinson's UK (G-4062)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, Lewy bodies, alpha-synuclein, cell transplantation, graft survival, pathogenesis, long-term graft function
- MeSH terms
- Humans, Immunohistochemistry, Parkinson Disease, Fetal Tissue Transplantation, Brain Tissue Transplantation, Lewy Bodies, Treatment Outcome, Disease Progression, alpha-Synuclein
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