Figure 1.

Schematic overview including the main pathological features of prodromal and classical α-synucleinopathies. The combination of novel structural and biochemical analyses have demonstrated the existence of different α-syn strains in classical α-synucleinopathies (PD, DLB and MSA). Recent experimental data also indicate that distinct α-syn strains might be associated, not only with the affected cell type and type of α-syn inclusion (neuronal LBs vs. oligodendroglial GCIs), but also with the neurodegeneration pattern and disease severity. However, at present it is still unclear whether distinct α-syn strains are also associated with prodromal α-synucleinopathies, or if they only constitute early phases of classical α-synucleinopathies. Thus, pathological α-syn in PAF and iRBD patients could lead to the formation of LBs, GCIs and the extension of neuronal loss to other areas within the CNS. SND, striatonigral degeneration; OPCA, olivopontocerebellar atrophy. Created with BioRender.com.