Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized 
by abnormal deposition of α-synuclein aggregates in many regions of the central 
and peripheral nervous systems. Accumulating evidence suggests that the 
α-synuclein pathology initiates in a few discrete regions and spreads to larger 
areas in the nervous system. Recent pathological studies of PD patients have 
raised the possibility that the enteric nervous system is one of the initial 
sites of α-synuclein aggregation and propagation. Here, we evaluated the 
induction and propagation of α-synuclein aggregates in the enteric nervous 
system of the A53T α-synuclein transgenic mice after injection of human brain 
tissue extracts into the gastric walls of the mice. Western analysis of the 
brain extracts showed that the DLB extract contained detergent-stable 
α-synuclein aggregates, but the normal brain extract did not. Injection of the 
DLB extract resulted in an increased deposition of α-synuclein in the myenteric 
neurons, in which α-synuclein formed punctate aggregates over time up to 4 
months. In these mice, inflammatory responses were increased transiently at 
early time points. None of these changes were observed in the A53T mice injected 
with saline or the normal brain extract, nor were these found in the wild type 
mice injected with the DLB extract. These results demonstrate that pathological 
α-synuclein aggregates present in the brain of DLB patient can induce the 
aggregation of endogenous α-synuclein in the myenteric neurons in A53T mice, 
suggesting the transmission of synucleinopathy lesions in the enteric nervous 
system.