Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson’s disease and dementia with Lewy bodies
Open accessAbstract
Extracellular α-synuclein has been proposed as a crucial mechanism for induction of pathological aggregate formation in previously healthy cells. In vitro, extracellular α-synuclein is partially associated with exosomal vesicles. Recently, we have provided evidence that exosomal α-synuclein is present in the central nervous system in vivo. We hypothesized that exosomal α-synuclein species from patients with α-synuclein related neurodegeneration serve as carriers for interneuronal disease transmission. We isolated exosomes from cerebrospinal fluid from patients with Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy as a non-α-synuclein related disorder that clinically overlaps with Parkinson’s disease, and neurological controls. Cerebrospinal fluid exosome numbers, α-synuclein protein content of cerebrospinal fluid exosomes and their potential to induce oligomerization of α-synuclein were analysed. The quantification of cerebrospinal fluid exosomal α-synuclein showed distinct differences between patients with Parkinson’s disease and dementia with Lewy bodies. In addition, exosomal α-synuclein levels correlated with the severity of cognitive impairment in cross-sectional samples from patients with dementia with Lewy bodies. Importantly, cerebrospinal fluid exosomes derived from Parkinson’s disease and dementia with Lewy bodies induce oligomerization of α-synuclein in a reporter cell line in a dose-dependent manner. Our data suggest that cerebrospinal fluid exosomes from patients with Parkinson’s disease and dementia with Lewy bodies contain a pathogenic species of α-synuclein, which could initiate oligomerization of soluble α-synuclein in target cells and confer disease pathology. Stuendl et al. show that CSF exosomes of patients with Parkinson’s disease or dementia with Lewy bodies contain α-synuclein and induce α-synuclein aggregation in a reporter cell line. Thus, exosomes may support inter-neuronal transmission of α-synuclein pathology. CSF exosomal α-synuclein may serve as a biomarker in α-synuclein-related neurodegeneration.
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Small extracellular vesicles isolated from cerebrospinal fluid can induce oligomerization of soluble α-syn in an in vitro model.
“Additional experiments were conducted, and these experiments showed that sEVs isolated from CSF can induce the oligomerization of soluble α-syn in an in vitro model [249].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [249]
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Cites
The prevalence of Parkinson's disease: a systematic review and meta-analysis
Pringsheim, T., Jette, N., Frolkis, A., & Steeves, T. D. L. (2014) · Movement Disorders · doi:10.1002/mds.25945 · Cited by 2,188 · see citing works
Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1746 · Cited by 1,845 · see citing works
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · see citing works
Exosomes are released by cultured cortical neurones
Fauré, J., Lachenal, G., Court, M., Hirrlinger, J., Chatellard-Causse, C., Blot, B., Grange, J., Schoehn, G., Goldberg, Y., Boyer, V., et al. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.12.003 · Cited by 896 · see citing works
Emerging roles of exosomes in neuron-glia communication
Frühbeis, C., Fröhlich, D., & Krämer-Albers, E.-M. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00119 · Cited by 275 · see citing works
Microglia in the aging brain: relevance to neurodegeneration
Luo, X.-G., Ding, J.-Q., & Chen, S.-D. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-12 · Cited by 236 · cited 2× · see citing works
“However, insufficient microglial clearance function, as observed in many neurodegenerative diseases, may pave the way for interneuronal propagation of pathogenic exosomal a-synuclein species (Luo et al., 2010).”
Flagged first, then by citations
Research works printed but not linked: 66
- Alvarez-Erviti L Seow Y Schapira AH Gardiner C Sargent IL Wood MJ Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 2011; 42: 360– 7. 21303699 PMC3107939
- Bellingham SA Guo BB Coleman BM Hill AF Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol 2012; 3: 124. 22563321 PMC3342525
- Braak H Del Tredici K Rub U de Vos RA Jansen Steur EN Braak E Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003a; 24: 197– 211. 12498954
- Braak H Rub U Gai WP Del Tredici K Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003b; 110: 517– 36. 12721813
- Danzer KM Kranich LR Ruf WP Cagsal-Getkin O Winslow AR Zhu L Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012a; 7: 42. 22920859 PMC3483256
- Danzer KM Kranich LR Ruf WP Cagsal-Getkin O Winslow AR Zhu L Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012b; 7: 42. 22920859 PMC3483256
- Danzer KM Krebs SK Wolff M Birk G Hengerer B Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem 2009; 111: 192– 203. 19686384
- Danzer KM Ruf WP Putcha P Joyner D Hashimoto T Glabe C Heat-shock protein 70 modulates toxic extracellular alpha-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J 2011; 25: 326– 36. 20876215 PMC3005424
- Desplats P Lee HJ Bae EJ Patrick C Rockenstein E Crews L Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 2009; 106: 13010– 5. 19651612 PMC2722313
- El-Agnaf OM Salem SA Paleologou KE Cooper LJ Fullwood NJ Gibson MJ Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 2003; 17: 1945– 7. 14519670
- El-Agnaf OM Salem SA Paleologou KE Curran MD Gibson MJ Court JA Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J 2006; 20: 419– 25. 16507759
- El Andaloussi S Lakhal S Mager I Wood MJ Exosomes for targeted siRNA delivery across biological barriers. Adv Drug Deliv Rev 2013; 65: 391– 7. 22921840
- Emmanouilidou E Elenis D Papasilekas T Stranjalis G Gerozissis K Ioannou PC Assessment of alpha-synuclein secretion in mouse and human brain parenchyma. PLoS One 2011; 6: e22225. 21779395 PMC3136497
- Fang Y Wu N Gan X Yan W Morrell JC Gould SJ Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 2007; 5: e158. 17550307 PMC1885833
- Fitzner D Schnaars M van Rossum D Krishnamoorthy G Dibaj P Bakhti M Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 2011; 124(Pt 3): 447– 58. 21242314
- Fruhbeis C Frohlich D Kuo WP Amphornrat J Thilemann S Saab AS Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 2013; 11: e1001604. 23874151 PMC3706306
- Gao L Tang H Nie K Wang L Zhao J Gan R Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson's disease diagnosis: a systematic review and meta-analysis. Int J Neurosci 2015; 125: 145– 54. 25202803
- Hansson O Hall S Ohrfelt A Zetterberg H Blennow K Minthon L Levels of cerebrospinal fluid alpha-synuclein oligomers are increased in Parkinson's disease with dementia and dementia with Lewy bodies compared to Alzheimer's disease. Alzheimers Res Ther 2014; 6: 25. 24987465 PMC4075410
- Hong Z Shi M Chung KA Quinn JF Peskind ER Galasko D DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 2010; 133(Pt 3): 713– 26. 20157014 PMC2842513
- Kang JH Irwin DJ Chen-Plotkin AS Siderowf A Caspell C Coffey CS Association of cerebrospinal fluid beta-amyloid 1-42, T-tau, P-tau181, and alpha-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 2013; 70: 1277– 87. 23979011 PMC4034348
- Kordower JH Brundin P Lewy body pathology in long-term fetal nigral transplants: is Parkinson's disease transmitted from one neural system to another? Neuropsychopharmacology 2009a; 34: 254. 19079079
- Kordower JH Brundin P Propagation of host disease to grafted neurons: accumulating evidence. Exp Neurol 2009b; 220: 224– 5. 19786018
- Kruse N Schulz-Schaeffer WJ Schlossmacher MG Mollenhauer B Development of electrochemiluminescence-based singleplex and multiplex assays for the quantification of alpha-synuclein and other proteins in cerebrospinal fluid. Methods 2012; 56: 514– 8. 22465793
- Kunadt M Eckermann K Stuendl A Gong J Russo B Strauss K Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation. Acta Neuropathol 2015; 129: 695– 713. 25778619 PMC4405286
- Lee HJ Bae EJ Lee SJ Extracellular alpha—synuclein-a novel and crucial factor in Lewy body diseases. Nat Rev Neurol 2014; 10: 92– 8. 24468877
- Lee HJ Patel S Lee SJ Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 2005; 25: 6016– 24. 15976091 PMC6724798
- Lee SJ Desplats P Lee HJ Spencer B Masliah E Cell-to-cell transmission of alpha-synuclein aggregates. Methods Mol Biol 2012; 849: 347– 59. 22528101 PMC4940116
- Li JY Englund E Widner H Rehncrona S Bjorklund A Lindvall O Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord 2010; 25: 1091– 6. 20198645
- Lippa CF Duda JE Grossman M Hurtig HI Aarsland D Boeve BF DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007; 68: 812– 9. 17353469
- Litvan I Agid Y Calne D Campbell G Dubois B Duvoisin RC Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47: 1– 9. 8710059
- Luk KC Kehm V Carroll J Zhang B O'Brien P Trojanowski JQ Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012a; 338: 949– 53. 23161999 PMC3552321
- Luk KC Kehm VM Zhang B O'Brien P Trojanowski JQ Lee VM Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice. J Exp Med 2012b; 209: 975– 86. 22508839 PMC3348112
- Luker KE Piwnica-Worms D Optimizing luciferase protein fragment complementation for bioluminescent imaging of protein-protein interactions in live cells and animals. Methods Enzymol 2004; 385: 349– 60. 15130748
- McKeith IG Dickson DW Lowe J Emre M O'Brien JT Feldman H Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005a; 65: 1863– 72. 16237129
- McKeith IG Dickson DW Lowe J Emre M O'Brien JT Feldman H Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005b; 65: 1863– 72. 16237129
- Mollenhauer B Cepek L Bibl M Wiltfang J Schulz-Schaeffer WJ Ciesielczyk B Tau protein, Abeta42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dement Geriatr Cogn Disord 2005; 19: 164– 70. 15637452
- Mollenhauer B El-Agnaf OM Marcus K Trenkwalder C Schlossmacher MG Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med 2010; 4: 683– 99. 20945981
- Mollenhauer B Locascio JJ Schulz-Schaeffer W Sixel-Doring F Trenkwalder C Schlossmacher MG alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011; 10: 230– 40. 21317042
- Mollenhauer B Schlossmacher MG CSF synuclein: adding to the biomarker footprint of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2010; 81: 590– 1. 20522867
- Mollenhauer B Trautmann E Otte B Ng J Spreer A Lange P alpha-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system. J Neural Transm 2012; 119: 739– 46. 22426833 PMC3378837
- Mollenhauer B Trautmann E Sixel-Doring F Wicke T Ebentheuer J Schaumburg M Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 2013a; 81: 1226– 34. 23997153
- Mollenhauer B Trautmann E Taylor P Manninger P Sixel-Doring F Ebentheuer J Total CSF alpha-synuclein is lower in de novo Parkinson patients than in healthy subjects. Neurosci Lett 2013b; 532: 44– 8. 23149132
- Montine TJ Shi M Quinn JF Peskind ER Craft S Ginghina C CSF Abeta and tau in Parkinson's disease with cognitive impairment. Mov Disord 2010; 25: 2682– 5. 20818673 PMC2978754
- Mougenot AL Nicot S Bencsik A Morignat E Verchere J Lakhdar L Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 2012; 33: 2225– 8. 21813214
- Muller CM de Vos RA Maurage CA Thal DR Tolnay M Braak H Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability. J Neuropathol Exp Neurol 2005; 64: 623– 8. 16042314
- Musiek ES Holtzman DM Origins of Alzheimer's disease: reconciling cerebrospinal fluid biomarker and neuropathology data regarding the temporal sequence of amyloid-beta and tau involvement. Curr Opin Neurol 2012; 25: 715– 20. 23041958 PMC3682920
- Noguchi-Shinohara M Tokuda T Yoshita M Kasai T Ono K Nakagawa M CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer's disease. Brain Res 2009; 1251: 1– 6. 19071095
- Nonaka T Watanabe ST Iwatsubo T Hasegawa M Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases. J Biol Chem 2010; 285: 34885– 98. 20805224 PMC2966103
- Ohrfelt A Grognet P Andreasen N Wallin A Vanmechelen E Blennow K Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett 2009; 450: 332– 5. 19022350
- Oosthuyzen W Sime NE Ivy JR Turtle EJ Street JM Pound J Quantification of human urinary exosomes by nanoparticle tracking analysis. J Physiol 2013; 591(Pt 23): 5833– 42. 24060994 PMC3872755
- Outeiro TF Putcha P Tetzlaff JE Spoelgen R Koker M Carvalho F Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One 2008; 3: e1867. 18382657 PMC2270899
- Popescu BO Toescu EC Popescu LM Bajenaru O Muresanu DF Schultzberg M Blood-brain barrier alterations in ageing and dementia. J Neurol Sci 2009; 283: 99– 106. 19264328
- Reesink FE Lemstra AW van Dijk KD Berendse HW van de Berg WD Klein M CSF alpha-synuclein does not discriminate dementia with Lewy bodies from Alzheimer's disease. J Alzheimers Dis 2010; 22: 87– 95. 20847452
- Schneider A Simons M Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res 2013; 352: 33– 47. 22610588 PMC3602607
- Shi M Liu C Cook TJ Bullock KM Zhao Y Ginghina C Plasma exosomal alpha-synuclein is likely CNS-derived and increased in Parkinson's disease. Acta Neuropathol 2014; 128: 639– 50. 24997849 PMC4201967
- Sokolova V Ludwig AK Hornung S Rotan O Horn PA Epple M Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces 2011; 87: 146– 50. 21640565
- Spillantini MG Crowther RA Jakes R Hasegawa M Goedert M alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci USA 1998; 95: 6469– 73. 9600990 PMC27806
- Strauss K Goebel C Runz H Mobius W Weiss S Feussner I Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann-Pick type C disease. J Biol Chem 2010; 285: 26279– 88. 20554533 PMC2924046
- Suzuki I Noguchi M Arito M Sato T Omoteyama K Maedomari M Serum peptides as candidate biomarkers for dementia with Lewy bodies. Int J Geriatr Psychiatry 2015; 30: 1195– 206. 25754375
- Tokuda T Qureshi MM Ardah MT Varghese S Shehab SA Kasai T Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010; 75: 1766– 72. 20962290
- Tokuda T Salem SA Allsop D Mizuno T Nakagawa M Qureshi MM Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. Biochem Biophys Res Commun 2006; 349: 162– 6. 16930553
- Ulusoy A Rusconi R Perez-Revuelta BI Musgrove RE Helwig M Winzen-Reichert B Caudo-rostral brain spreading of alpha-synuclein through vagal connections. EMBO Mol Med 2013; 5: 1051– 9. 23703938 PMC3721477
- van der Pol E Coumans FA Grootemaat AE Gardiner C Sargent IL Harrison P Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 2014; 12: 1182– 92. 24818656
- Vidal M Mangeat P Hoekstra D Aggregation reroutes molecules from a recycling to a vesicle-mediated secretion pathway during reticulocyte maturation. J Cell Sci 1997; 110 (Pt 16): 1867– 77. 9296387
- Volpicelli-Daley LA Luk KC Patel TP Tanik SA Riddle DM Stieber A Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011; 72: 57– 71. 21982369 PMC3204802
- Zhuang X Xiang X Grizzle W Sun D Zhang S Axtell RC Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19: 1769– 79. 21915101 PMC3188748
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- Authors
- Stuendl, A., Kunadt, M., Kruse, N., Bartels, C., Moebius, W., Danzer, K. M., Mollenhauer, B., & Schneider, A.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Universität Ulm (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Schneider, Anja
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-12-08
- Volume
- 139
- Issue
- 2
- Pages
- 481-494
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC4805087
- OpenAlex
- W2276360944
- Cited by
- 428
- References
- 6
- Citations by year
- 2026: 28 · 2025: 29 · 2024: 39 · 2023: 39 · 2022: 47 · 2021: 71 · 2020: 52 · 2019: 47 · 2018: 30 · 2017: 28 · 2016: 18
- FWCI
- 17.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brain (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- DZNE Pub (submittedVersion, cc-by-nc)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Teva Pharmaceutical Industries
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, exosomes, cerebrospinal fluid, Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, protein aggregation, oligomerization, biomarkers, cognitive impairment
- MeSH terms
- Cerebrospinal Fluid, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Parkinson Disease, Cohort Studies, Lewy Body Disease, alpha-Synuclein, Exosomes, Protein Aggregates
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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