Lewy body pathology in fetal grafts

Abstract

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.