4.6 Article

Characterization of Lewy Body Pathology in 12-and 16-Year-Old Intrastriatal Mesencephalic Grafts Surviving in a Patient With Parkinson's Disease

Journal

MOVEMENT DISORDERS
Volume 25, Issue 8, Pages 1091-1096

Publisher

WILEY
DOI: 10.1002/mds.23012

Keywords

neural transplantation; Lewy body; protein aggregation; alpha-synuclein; transmissible neurological disease

Funding

  1. Swedish Research Council
  2. Swedish Parkinson Foundation
  3. Nordic Center of Excellence on Neurodegeneration
  4. Strong Research Environment of the Swedish Research Council (NeuroFortis)
  5. Linne grant (BAGADI-LICO)
  6. Segerfalk Foundation
  7. Michael J. Fox Foundation
  8. Lund University
  9. Swedish Alzheimer Foundation

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We previously reported the occurrence of Lewy bodies in grafted human fetal mesencephalic neurons in two patients with Parkinson's disease. Here, we have used immunohistochemistry and electron microscopy to characterize the development of Lewy bodies in one of these cases. This patient was operated in putamen on both sides at 12 or 16 years before death, respectively. We demonstrate that 2% of the 12-year-old and 5% of the 16-year-old grafted, presumed dopaminergic neurons contained Lewy bodies immunoreactive for alpha-synuclein. Based on morphological analysis, two forms of alpha-synuclein-positive aggregates were distinguished in the grafts, the first a classical and compact Lewy body, the other a loose meshwork aggregate. Lewy bodies in the grafts stained positively for ubiquitin and thioflavin-S, and contained characteristic re-synuclein immunoreactive electron dense fibrillar structures on electron microscopy. Our data indicate that Lewy bodies develop gradually in transplanted dopaminergic neurons in a fashion similar to that in dopaminergic neurons in the host substantia nigra. (C) 2010 Movement Disorder Society

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