Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates - Archive ouverte HAL Access content directly
Journal Articles Science Advances Year : 2020

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

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Nicolas P. Rougier
Sylvain Bohic
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  • PersonId : 838924
Christophe Sandt
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  • PersonId : 1019719
Brit Mollenhauer
Miquel Vila
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  • PersonId : 958285

Abstract

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates (termed ‘Lewy bodies’), is a well-established characteristic of Parkinson’s 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 LBs, 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.
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hal-02611441 , version 1 (18-05-2020)

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Mathieu Bourdenx, Aurélien Nioche, Sandra Dovero, Marie-Laure Arotcarena, Sandrine M. J. Camus, et al.. Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates. Science Advances , 2020, 6 (20), pp.eaaz9165. ⟨10.1126/sciadv.aaz9165⟩. ⟨hal-02611441⟩
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