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In Parkinson's disease, some of the first alpha-synuclein aggregates appear in the olfactory system and the dorsal motor nucleus of the vagus nerve before spreading to connected brain regions. We previously demonstrated that injection of alpha-synuclein fibrils unilaterally into the olfactory bulb of wild type mice leads to widespread synucleinopathy in brain regions directly and indirectly connected to the injection site, consistently, over the course of periods longer than 6 months. Our previously reported observations support the idea that alpha-synuclein inclusions propagates between brain region through neuronal networks. In the present study, we further defined the pattern of propagation of alpha-synuclein inclusions and developed a mathematical model based on known mouse brain connectivity. Using this model, we first predicted the pattern of alpha-synuclein inclusions propagation following an injection of …