Temporal evolution of microglia and α-synuclein accumulation following foetal grafting in Parkinson's disease

Abstract

We observed Lewy pathology in healthy embryonic dopamine neurons implanted into the striatum of patients with advanced Parkinson's disease. In the present study we examined the temporal relationship between the presence of inflammation with activated microglia and the emergence of α-synuclein pathology. Inflammation with activated microglia was observed in all grafts and at all time points examined between 18 months and 16 years as determined by both CD45 and TMEM119 staining. In contrast, α-synuclein was not detected at 18 months, only diffuse monomeric α-synuclein staining was observed at 4 years, and α-synuclein aggregates were not observed until 14-16 years after transplantation. Thus, there is evidence of inflammation and microglial activation in graft deposits long before the accumulation of α-synuclein pathology in implanted dopamine neurons. These observations raise the possibility that microglial activation contributes to the development of α-synuclein pathology, and supports the concept that microglia play an integral role in the propagation and spread of α-synuclein pathology.