Intracellular a-synuclein assemblies suffice to alter nanoscale diffusion in the striatal extracellular space

Neurodegeneration in a-synucleinopathies involves the spread of α-synuclein aggregates through the extracellular space (ECS). Single-particle tracking studies showed that α-synuclein-induced neurodegeneration increases ECS molecular diffusivity. To disentangle the consequences of neuronal loss versus intracellular aggregate formation, we tracked single-walled carbon nanotubes to characterise ECS rheology in the striatum of mouse models of synucleinopathies. We showed that intracellular α-synuclein aggregates, without neurodegeneration, suffice to alter nanoscale diffusion in the striatum ECS.