We characterized a novel model of prodromal Parkinson’s disease (PD) induced by inoculating human alpha-synuclein into the olfactory bulb to trigger alpha-synucleinopathy in wildtype mice. Inoculums were obtained from post-mortem human temporal cortex tissues by sucrose gradient fractionation. C57Bl/6J male mice were inoculated with Lewy Body (LB)-containing fractions (hsyn+) from patients with idiopathic PD; control-injected mice were inoculated with non-LB PD fractions (hsyn-), aggregated non-toxic fractions from non-PD patients (hCtrl), or the corresponding vehicle (Veh). Mice were evaluated in a series of odour and motor tasks at 4- and 8- months post-injection (mpi) and ex vivo for spatial distribution of alpha-synuclein in brain regions. hsyn+-injected mice showed mild deficits in olfactory function, discrimination, and progressive dishabituation to odours without robust differences in fine motor dexterity or neuropsychiatric performance. Histopathology corroborated the spatial and temporal distribution of pSer129-synuclein immunoreactivity throughout the brain in hsyn+ animals. At 4 mpi, pathology extended to distal ipsilateral and contralateral structures located one or two synapses away from the olfactory injection sites, including entorhinal and perirhinal cortices, amygdala nuclei and hippocampus. By 8 mpi., alpha-synuclein pathology had increased in severity and had progressed to other brain regions (including cortical associative and secondary cortical brain regions). We provide the first evidence of a model with specific olfactory deficits and neuropathology, at anatomical and histological levels, that is faithful and most translationally relevant to prodromal PD in human. Its slow progression will allow for the exploration of therapeutic strategies targeting disease modifications and early prodromal treatment