neurons and lead to their degeneration. Two theories for the selective vulnerability of neuronal populations in Parkinson’s disease currently exist: the “spread Lewy pathology model” which assumes cell-to-cell contacts enabling spreading of prion-like α-synuclein aggregates 62; and the “threshold theory” 63,64 which proposes that the vulnerable cell types degenerate due to molecular/functional biological similarities in a cell-autonomous fashion. While both theories are compatible and can co-exist, our findings support the existence of cell autonomous mechanisms contributing to selective vulnerability. We caution that we do not know if all cholinergic and monoaminergic neurons show degeneration or functional impairment. However, analysis of the cellular mechanisms driving the association of cholinergic and monoaminergic neurons with Parkinson’s disease revealed endosomal trafficking as a plausible common pathogenic mechanism.
