Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in non-human primates

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates (termed 9Lewy bodies9), is a well-established characteristic of Parkinson9s disease. Much evidence, accumulated from multiple experimental models has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from PD patients. Unexpectedly, our results show that, in non-human primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the Lewy Bodies, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD as multiple causes can induce similar outcome regarding dopaminergic neurodegeneration.