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

M. Bourdenx, A. Nioche, S. Dovero, M. L. Arotcarena, S. Camus, G. Porras, M. L. Thiolat, N. P. Rougier, A. Prigent, P. Aubert, S. Bohic, C. Sandt, F. Laferrière, E. Doudnikoff, N. Kruse, B. Mollenhauer, S. Novello, M. Morari, T. Leste-Lasserre, I. Trigo DamasM. Goillandeau, C. Perier, C. Estrada, N. Garcia-Carrillo, A. Recasens, N. N. Vaikath, O. M.A. El-Agnaf, M. T. Herrero, P. Derkinderen, M. Vila, J. A. Obeso, B. Dehay*, E. Bezard

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)

Abstract

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). 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 patients with PD. Unexpectedly, our results show that, in nonhuman 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 a similar outcome regarding dopaminergic neurodegeneration.

Original languageEnglish
Article numbereaaz9165
JournalScience Advances
Volume6
Issue number20
DOIs
Publication statusPublished - May 2020
MoE publication typeA1 Journal article-refereed

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