Lewy body pathology in fetal grafts.
Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [(18)F]6-fluroro-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) uptake and improved motor function in open-label assessments have failed to establish any clinical benefits in double-blind, sham-controlled studies. To understand morphological and neurochemical alterations of grafted neurons, we performed postmortem analyses on six Parkinson's disease (PD) patients who had received fetal tissue transplantation 18-19 months, 4 years, and 14 years previously. These studies revealed robust neuronal survival with normal dopaminergic phenotypes in 18-month-old grafts and decreased dopamine transporter and increased cytoplasmic alpha-synuclein in 4-year-old grafts. We also found a decline of both dopamine transporter and tyrosine hydroxylase and the formation of Lewy body-like inclusions in 14-year-old grafts, which stained positive for alpha-synuclein and ubiquitin proteins. These pathological changes suggest that PD is an ongoing process that affects grafted cells in the striatum in a manner similar to how resident dopamine neurons are affected in the substantia nigra.
Chu
Yaping
Y
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Kordower
Jeffrey H
JH
D000818:Animals; D003342:Corpus Striatum / Q000601:surgery; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation / Q000473:pathology; D005333:Fetus / Q000473:pathology*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006085:Graft Survival; D006801:Humans; D007553:Isotope Labeling; D016631:Lewy Bodies / Q000473:pathology*; D008543:Melanins / Q000378:metabolism; D011247:Pregnancy; D013378:Substantia Nigra / Q000473:pathology / Q000637:transplantation; D051844:alpha-Synuclein / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008543:Melanins; D051844:alpha-Synuclein; C014121:neuromelanin; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine