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Parkinson’s disease (PD) is an age-related neurodegenerative disorder that harbors an enigmatic neuropathologic change known as Lewy-related pathology. Defined as proteinaceous intracellular inclusions containing α-synuclein, the spread of Lewy-related pathology across cortical regions is associated with cognitive dysfunction. However, the relationship between Lewy-related pathology, neurodegeneration, and the onset of dementia in PD is poorly understood. The work described in this dissertation sought to clarify this relationship though the in vivo application of α-synuclein pre-formed fibrils (PFF) to model Lewy-related pathology in the mouse forebrain. Towards this, we performed stereotactic injection of α-synuclein PFF under several experimental paradigms. In a bilateral hippocampal/cortical injection paradigm, we evaluated the accumulation of α-synuclein pathology and hippocampal …