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The cellular hallmarks of Parkinsons disease(PD)are the loss of nigral dopamine neurons and the formation of α-synuclein-enriched Lewy body and Lewy neurites in the remaining neurons.Based on the topographic distribution of Lewy bodies established after autopsy of brains from people with PD,Braak and coworkers hypothesized that Lewy pathology primes in the enteric nervous system and spreads to the brain,suggesting an active retrograde transport of α-synuclein (the key protein component in Lewy bodies),via the vagal nerve.This hypothesis however has not yet been tested experimentally.Here,we use the human PD brain lysate enriched with different forms of α-synuclein and monomeric,oligomeric and fibrillar recombinant α-synuclein in an in vivo animal model to test the hypothesis.We demonstrate that α-synuclein present in the human PD brain lysate is transported via the vagal nerve,and reach the dorsal motor nucleus of the vagus in the brainstem in a time-dependent manner after injection into the intestinal wall.Monomeric,oligomeric and fibrillar α-synuclein exhibit identical transport pattern from the intestine to the brain.Moreover,using live cell imaging,we determine that both slow and fast components of axonal transport are involved in the transport of aggregated α-synuclein.To our best knowledge,this is the first study providing direct evidence that α-synuclein species can propagate from the guts to the brain,and that both slow and fast axonal transport are involved in the neuronal translocation of α-synuclein.