Temporal evolution of microglia and α-synuclein accumulation following foetal grafting in Parkinson's disease.
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.
['Olanow|C Warren|CW|', 'Savolainen|Mari|M|', 'Chu|Yaping|Y|', 'Halliday|Glenda M|GM|', 'Kordower|Jeffrey H|JH|']
D000818:Animals D059290:Dopaminergic Neurons D006801:Humans D007249:Inflammation D008262:Macrophage Activation D008565:Membrane Proteins D008822:Mice, Transgenic D017628:Microglia D010300:Parkinson Disease D051844:alpha-Synuclein
microglia α-synuclein Parkinson’s disease