In synucleinopathies alpha-synuclein (αsyn) aggregates and spreads in the brain in a prion-like manner, affecting different cells and brain regions depending on the disease ; resulting in distinct histopathological and clinical features. However the mechanisms underlying the selective vulnerability and tropism for different cell populations remain unknown. We know that αsyn can misfold and acquire different conformations, generating polymorphs / strains that can propagate. These strains can be produced in vitro but also amplified from human brains with synucleinopathies. We have previously demonstrated that different strains (produced in vitro or amplified from post-mortem brain tissue) are able to propagate differently in cell culture and in rodents brains. We now hypothesize that the selectivity of pathological asyn for specific cellular populations relies notably on strain-specific interactions with intracellular and membrane proteins. Using proteomic approaches, we investigate strain-specific interactomes in different cellular populations. Our aim is to determine which interactions play key roles in strain-specific and selective propagation of pathological αsyn, and to select potential interactors to target in order to prevent or limit the transmission/ amplification of αsyn strains.