D. Aarsland, J. Zaccai, and C. Brayne, A systematic review of prevalence studies of dementia in Parkinson's disease, Mov Disord, vol.20, pp.1255-1263, 2005.

I. Ahmed, R. Tamouza, M. Delord, R. Krishnamoorthy, C. Tzourio et al., Association between Parkinson's disease and the HLA-DRB1 locus, Mov Disord, vol.27, pp.1104-1110, 2012.

I. Alafuzoff, T. Arzberger, S. Al-sarraj, I. Bodi, N. Bogdanovic et al., Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium, Brain Pathol, vol.18, pp.484-496, 2008.

I. Alafuzoff, P. G. Ince, T. Arzberger, S. Al-sarraj, J. Bell et al., Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium, Acta Neuropathol, vol.117, pp.635-652, 2009.

V. Baekelandt, A. Claeys, K. Eggermont, E. Lauwers, D. Strooper et al., Characterization of lentiviral vectormediatedgene transfer in adult mouse brain, Human Gene Therapy, vol.13, issue.7, p.19, 2002.

T. Bartels, J. G. Choi, and D. J. Selkoe, ?-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation, Nature, vol.477, pp.107-110, 2011.

J. T. Bendor, T. P. Logan, and R. H. Edwards, The function of ?-synuclein, Neuron, vol.79, pp.1044-1066, 2013.

M. E. Bernis, J. T. Babila, S. Breid, K. A. Wusten, U. Wullner et al., Prion-like propagation of human brain-derived alpha-synuclein in transgenic mice expressing human wild-type alpha-synuclein, Acta Neuropathol Commun, vol.3, p.75, 2015.

L. Bousset, L. Pieri, G. Ruiz-arlandis, J. Gath, P. H. Jensen et al., Structural and functional characterization of two alpha-synuclein strains, Nat Commun, vol.4, p.2575, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01183047

J. C. Bridi and F. Hirth, Mechanisms of ?-synuclein induced synaptopathy in Parkinson's disease, Front Neurosci, vol.12, p.80, 2018.

N. Candelise, M. Schmitz, F. Llorens, A. Villar-pique, M. Cramm et al., Seeding variability of different alpha synuclein strains in synucleinopathies, Ann Neurol, vol.85, pp.691-703, 2019.

M. C. Chartier-harlin, J. Kachergus, C. Roumier, V. Mouroux, X. Douay et al., Alpha-synuclein locus duplication as a cause of familial Parkinson's disease, Lancet, vol.364, pp.1167-1169, 2004.

K. A. Conway, S. J. Lee, J. C. Rochet, T. T. Ding, R. E. Williamson et al., Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy, Proc Natl Acad Sci, vol.97, pp.571-576, 2000.

F. Degorce, A. Card, S. Soh, E. Trinquet, G. P. Knapik et al., HTRF: A technology tailored for drug discovery-a review of theoretical aspects and recent applications, Curr Chem Genomics, vol.3, pp.22-32, 2009.

P. Desplats, H. J. Lee, E. J. Bae, C. Patrick, E. Rockenstein et al., Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein, Proc Natl Acad Sci, vol.106, pp.13010-13015, 2009.

A. Fenyi, A. Coens, T. Bellande, R. Melki, and L. Bousset, Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces, Sci Rep, vol.8, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01871856

A. Fenyi, L. Leclair-visonneau, T. Clairembault, E. Coron, M. Neunlist et al., Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification, Neurobiol Dis, vol.129, pp.38-43, 2019.
URL : https://hal.archives-ouvertes.fr/cea-02279266

S. Gilman, G. K. Wenning, P. A. Low, D. J. Brooks, C. J. Mathias et al., Second consensus statement on the diagnosis of multiple system atrophy, Neurology, vol.71, pp.670-676, 2008.

M. Goedert, Alpha-synuclein and neurodegenerative diseases, Nat Rev Neurosci, vol.2, pp.492-501, 2001.

M. Goedert, Parkinson's disease and other alpha-synucleinopathies, Clin Chem Lab Med, vol.39, pp.308-312, 2001.

S. Gribaudo, P. Tixador, L. Bousset, A. Fenyi, P. Lino et al., Propagation of alpha-synuclein strains within human reconstructed neuronal network, Stem Cell Reports, vol.12, p.7, 2018.

V. Grozdanov, L. Bousset, M. Hoffmeister, C. Bliederhaeuser, C. Meier et al., Increased immune activation by pathologic alpha-synuclein in Parkinson's disease, Ann Neurol, 2019.

C. Hansen, E. Angot, A. L. Bergström, J. A. Steiner, L. Pieri et al., ) ?-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells, J Clin Invest, vol.121, pp.715-725, 2011.

P. Hobson and J. Meara, Risk and incidence of dementia in a cohort of older subjects with Parkinson's disease in the United Kingdom, Mov Disord, vol.19, pp.1043-1049, 2004.

J. H. Kordower, Y. Chu, R. A. Hauser, T. B. Freeman, and C. W. Olanow, Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease, Nat Med, vol.14, pp.504-506, 2008.

A. Lau, R. So, H. Lau, J. C. Sang, A. Ruiz-riquelme et al., ) alpha-Synuclein strains target distinct brain regions and cell types, Nat Neurosci, 2019.

J. Y. Li, E. Englund, J. L. Holton, D. Soulet, P. Hagell et al., Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation, Nat Med, vol.14, pp.501-503, 2008.

K. C. Luk, V. Kehm, J. Carroll, B. Zhang, P. O'brien et al., Pathological ?-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice, Science, vol.338, pp.949-953, 2012.

K. C. Luk, C. Song, P. O'brien, A. Stieber, J. R. Branch et al., Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells, Proc Natl Acad Sci, vol.106, 2009.

M. Masuda-suzukake, T. Nonaka, M. Hosokawa, T. Oikawa, T. Arai et al., Prion-like spreading of pathological alpha-synuclein in brain, Brain, vol.136, pp.1128-1138, 2013.

M. Masuda-suzukake, T. Nonaka, M. Hosokawa, T. Oikawa, T. Arai et al., Prion-like spreading of pathological ?-synuclein in brain, Brain, vol.136, pp.1128-1138, 2013.

I. G. Mckeith, D. Galasko, K. Kosaka, E. K. Perry, D. W. Dickson et al., Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop, vol.47, pp.1113-1124, 1996.

M. K. Nam, J. H. Han, J. Y. Jang, S. E. Yun, G. Y. Kim et al., A novel link between the conformations, exposure of specific epitopes, and subcellular localization of ?-synuclein, Biochim Biophys Acta, vol.1850, pp.2497-2505, 2015.

T. Nonaka, S. T. Watanabe, T. Iwatsubo, and M. Hasegawa, Seeded aggregation and toxicity of ?-synuclein and tau: cellular models of neurodegenerative diseases, J Biol Chem, vol.285, pp.34885-34898, 2010.

K. E. Paleologou, C. L. Kragh, D. M. Mann, S. A. Salem, R. Al-shami et al., Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies, Brain, vol.132, pp.1093-1101, 2009.

W. Peelaerts, L. Bousset, A. Van-der-perren, A. Moskalyuk, R. Pulizzi et al., ) ?-Synuclein strains cause distinct synucleinopathies after local and systemic administration, Nature, vol.522, pp.340-344, 2015.

C. Peng, R. J. Gathagan, D. J. Covell, C. Medellin, A. Stieber et al., Cellular milieu imparts distinct pathological ?-synuclein strains in ?-synucleinopathies, Nature, vol.557, pp.558-563, 2018.

A. Van-der-perren, F. Macchi, J. Toelen, M. Carlon, M. Maris et al., FK506 reduces neuroinflammation and dopaminergic neurodegeneration in an ?-synuclein-based rat model for Parkinson's disease, Neurobiol Aging, vol.36, pp.1559-1568, 2015.

A. Van-der-perren, J. Toelen, M. Carlon, C. Van-den-haute, and F. Coun, Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9, Gene Ther, vol.18, pp.517-527, 2011.

A. Van-der-perren, J. Toelen, C. Casteels, F. Macchi, A. S. Van-rompuy et al., Longitudinal follow-up and characterization of a robust rat model for Parkinson's disease based on overexpression of alpha-synuclein with adeno-associated viral vectors, Neurobiol Aging, vol.36, pp.1543-1558, 2015.

L. Pieri, K. Madiona, L. Bousset, and R. Melki, Fibrillar alphasynuclein and huntingtin exon 1 assemblies are toxic to the cells, Biophys J, vol.102, pp.2894-2905, 2012.

M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia et al., Mutation in the alpha-synuclein gene identified in families with Parkinson's disease, Science, vol.276, pp.2045-2047, 1997.

R. B. Postuma, D. Berg, M. Stern, W. Poewe, C. W. Olanow et al., MDS clinical diagnostic criteria for Parkinson's disease, Mov Disord, vol.30, pp.1591-1601, 2015.

S. B. Prusiner, A. L. Woerman, D. A. Mordes, J. C. Watts, R. Rampersaud et al., Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism, Proc Natl Acad Sci, vol.112, pp.5308-5317, 2015.

A. Recasens, B. Dehay, J. Bové, I. Carballo-carbajal, S. Dovero et al., Lewy body extracts from Parkinson disease brains trigger ?-synuclein pathology and neurodegeneration in mice and monkeys, Ann Neurol, vol.75, pp.351-362, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-02439340

C. Schmitz and P. R. Hof, Designed-based stereology in neuroscience, Neuroscience, vol.130, issue.4, pp.813-844, 2005.

M. Shahnawaz, A. Mukherjee, S. Pritzkow, N. Mendez, P. Rabadia et al., Discriminating ?-synuclein strains in Parkinson's disease and multiple system atrophy, 2020.

A. N. Shrivastava, L. Bousset, M. Renner, V. Redeker, J. Savistchenko et al., Differential membrane binding and seeding of distinct alpha-synuclein fibrillar polymorphs, Biophys J, vol.118, pp.1301-1320, 2020.
URL : https://hal.archives-ouvertes.fr/cea-02480815

A. N. Shrivastava, V. Redeker, N. Fritz, L. Pieri, L. G. Almeida et al., ) alpha-synuclein assemblies sequester neuronal alpha3-Na+/K+-ATPase and impair Na+ gradient, EMBO J, vol.34, pp.2408-2423, 2015.

Z. A. Sorrentino, M. S. Goodwin, C. J. Riffe, J. S. Dhillon, Y. Xia et al., Unique alpha-synuclein pathology within the amygdala in Lewy body dementia: implications for disease initiation and progression, Acta Neuropathol Commun, vol.7, p.142, 2019.

M. G. Spillantini, M. L. Schmidt, V. M. Lee, J. Q. Trojanowski, R. Jakes et al., Alpha-synuclein in Lewy bodies, Nature, vol.388, pp.839-840, 1997.

T. Strohaker, B. C. Jung, S. H. Liou, C. O. Fernandez, D. Riedel et al., Structural heterogeneity of alpha-synuclein fibrils amplified from patient brain extracts, Nat Commun, vol.10, p.5535, 2019.

Z. Sultana, K. E. Paleologou, K. M. Al-mansoori, M. T. Ardah, N. Singh et al., Dynamic modeling of ?-synuclein aggregation in dopaminergic neuronal system indicates points of neuroprotective intervention: experimental validation with implications for Parkinson's therapy, Neuroscience, vol.199, pp.303-317, 2011.

D. Sulzer, R. N. Alcalay, F. Garretti, L. Cote, E. Kanter et al., T cells from patients with Parkinson's disease recognize alpha-synuclein peptides, Nature, vol.546, pp.656-661, 2017.

J. Sun, L. Wang, H. Bao, S. Premi, U. Das et al., Functional cooperation of alpha-synuclein and VAMP2 in synaptic vesicle recycling, Proc Natl Acad Sci, vol.116, pp.11113-11115, 2019.

P. Thakur, L. S. Breger, M. Lundblad, O. W. Wan, B. Mattsson et al., Modeling Parkinson's disease pathology by combination of fibril seeds and alpha-synuclein overexpression in the rat brain, Proc Natl Acad Sci, vol.114, pp.8284-8293, 2017.

F. X. Theillet, A. Binolfi, B. Bekei, A. Martorana, H. M. Rose et al., Structural disorder of monomeric ?-synuclein persists in mammalian cells, Nature, vol.530, pp.45-50, 2016.

L. A. Volpicelli-daley, K. C. Luk, T. P. Patel, S. A. Tanik, D. M. Riddle et al., Exogenous ?-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death, Neuron, vol.72, pp.57-71, 2011.

K. Wakabayashi, S. Hayashi, A. Kakita, M. Yamada, Y. Toyoshima et al., Accumulation of alpha-synuclein/ NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy, Acta Neuropathol, vol.96, pp.445-452, 1998.

K. Wakabayashi, M. Yoshimoto, S. Tsuji, and H. Takahashi, Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy, Neurosci Lett, vol.249, pp.180-182, 1998.

L. Wang, U. Das, D. A. Scott, Y. Tang, P. J. Mclean et al., alpha-synuclein multimers cluster synaptic vesicles and attenuate recycling, Curr Biol, vol.24, pp.2319-2326, 2014.

L. Wang, U. Das, D. A. Scott, Y. Tang, P. J. Mclean et al., ?-synuclein multimers cluster synaptic vesicles and attenuate recycling, Curr Biol, vol.24, pp.2319-2326, 2014.

J. C. Watts, K. Giles, A. Oehler, L. Middleton, D. T. Dexter et al., Transmission of multiple system atrophy prions to transgenic mice, Proc Natl Acad Sci, vol.110, pp.19555-19560, 2013.

B. Winner, R. Jappelli, S. K. Maji, P. A. Desplats, L. Boyer et al., In vivo demonstration that alpha-synuclein oligomers are toxic, Proc Natl Acad Sci, vol.108, pp.4194-4199, 2011.

J. J. Zarranz, J. Alegre, J. C. Gómez-esteban, E. Lezcano, R. R. Ampuero et al., The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia, Ann Neurol, vol.55, pp.164-173, 2004.

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