PT  - JOURNAL ARTICLE
AU  - M. Bourdenx
AU  - A. Nioche
AU  - S. Dovero
AU  - M.-L. Arotcarena
AU  - S. Camus
AU  - G. Porras
AU  - M.-L. Thiolat
AU  - N. P. Rougier
AU  - A. Prigent
AU  - P. Aubert
AU  - S. Bohic
AU  - C. Sandt
AU  - F. Laferrière
AU  - E. Doudnikoff
AU  - N. Kruse
AU  - B. Mollenhauer
AU  - S. Novello
AU  - M. Morari
AU  - T. Leste-Lasserre
AU  - I. Trigo Damas
AU  - M. Goillandeau
AU  - C. Perier
AU  - C. Estrada
AU  - N. Garcia-Carrillo
AU  - A. Recasens
AU  - N. N. Vaikath
AU  - O. M. A. El-Agnaf
AU  - M. Trinidad Herrero
AU  - P. Derkinderen
AU  - M. Vila
AU  - J. A. Obeso
AU  - B. Dehay
AU  - E. Bezard
TI  - Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in non-human primates
AID  - 10.1101/825216
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 825216
4099  - http://biorxiv.org/content/early/2019/10/31/825216.short
4100  - http://biorxiv.org/content/early/2019/10/31/825216.full
AB  - 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.