Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies

Brain

Volumn 139, Issue 2, 2016, Pages 481-494

  Stuendl, Anne ^a,b   Kunadt, Marcel ^a,b,c   Kruse, Niels ^a   Bartels, Claudia ^a   Moebius, Wiebke ^b   Danzer, Karin M ^d   Mollenhauer, Brit ^a,e   Schneider, Anja ^a,b,c,f  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b MAX PLANCK INSTITUTE OF EXPERIMENTAL MEDICINE   (Germany)

^c Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)   (Germany)

^d UNIVERSITY OF ULM   (Germany)

^e PARACELSUS ELENA KLINIK   (Germany)

^f GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

Author keywords

cerebrospinal fluid; exosomes; extracellular vesicles; Parkinson's disease; synuclein

Indexed keywords

ALPHA SYNUCLEIN; PROTEIN AGGREGATE;

ARTICLE; CELL ISOLATION; CEREBROSPINAL FLUID ANALYSIS; COGNITIVE DEFECT; CONTROLLED STUDY; DIFFUSE LEWY BODY DISEASE; EXOSOME; HUMAN; HUMAN CELL; OLIGOMERIZATION; PARKINSON DISEASE; PRIORITY JOURNAL; PROGRESSIVE SUPRANUCLEAR PALSY; PROTEIN AGGREGATION; PROTEIN CONTENT; BIOSYNTHESIS; CEREBROSPINAL FLUID; COHORT ANALYSIS; CROSS-SECTIONAL STUDY; FEMALE; FOLLOW UP; LONGITUDINAL STUDY; MALE; METABOLISM; PHYSIOLOGY;

ALPHA-SYNUCLEIN; CEREBROSPINAL FLUID; COHORT STUDIES; CROSS-SECTIONAL STUDIES; EXOSOMES; FEMALE; FOLLOW-UP STUDIES; HUMANS; LEWY BODY DISEASE; LONGITUDINAL STUDIES; MALE; PARKINSON DISEASE; PROTEIN AGGREGATES;

EID: 84977123370     PISSN: 00068950     EISSN: 14602156     Source Type: Journal    
DOI: 10.1093/brain/awv346     Document Type: Article

References (72)

1. Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, et al. Lysosomal dysfunction increases exosome-mediated alphasynuclein release and transmission. Neurobiol Dis 2011; 42: 360-7
2. 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
3. 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
4. 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
5. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012a; 7: 42
6. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012b; 7: 42
7. 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
8. Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, et al. Heat-shock protein 70 modulates toxic extracellular alphasynuclein oligomers and rescues trans-synaptic toxicity. FASEB J 2011; 25: 326-36
9. Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, et al. Inclusion formation and neuronal cell death through neuron-toneuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 2009; 106: 13010-5
10. El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, Gibson MJ, et al. Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 2003; 17: 1945-7
11. El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, et al. 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
12. 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
13. Emmanouilidou E, Elenis D, Papasilekas T, Stranjalis G, Gerozissis K, Ioannou PC, et al. Assessment of alpha-synuclein secretion in mouse and human brain parenchyma. PLoS One 2011; 6: e22225
14. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010; 30: 6838-51
15. 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
16. Faure J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006; 31: 642-8
17. Fitzner D, Schnaars M, van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, et al. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 2011; 124(Pt 3): 447-58
18. Fruhbeis C, Frohlich D, Kramer-Albers EM. Emerging roles of exosomes in neuron-glia communication. Front Physiol 2012; 3: 119
19. Fruhbeis C, Frohlich D, Kuo WP, Amphornrat J, Thilemann S, Saab AS, et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 2013; 11: e1001604
20. Gao L, Tang H, Nie K, Wang L, Zhao J, Gan R, et al. 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
21. Hansson O, Hall S, Ohrfelt A, Zetterberg H, Blennow K, Minthon L, et al. 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
22. Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 2010; 133(Pt 3): 713-26
23. Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS, et al. 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
24. 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
25. Kordower JH, Brundin P. Propagation of host disease to grafted neurons: accumulating evidence. Exp Neurol 2009b; 220: 224-5
26. 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
27. Kunadt M, Eckermann K, Stuendl A, Gong J, Russo B, Strauss K, et al. Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation. Acta Neuropathol 2015; 129: 695-713
28. 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
29. Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 2005; 25: 6016-24
30. 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
31. Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008; 14: 501-3
32. Li JY, Englund E, Widner H, Rehncrona S, Bjorklund A, Lindvall O, et al. Characterization of Lewy body pathology in 12-and 16-yearold intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord 2010; 25: 1091-6
33. Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF, et al. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007; 68: 812-9
34. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. 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
35. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, et al. Pathological alpha-synuclein transmission initiates Parkinsonlike neurodegeneration in nontransgenic mice. Science 2012a; 338: 949-53
36. 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
37. 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
38. Luo XG, Ding JQ, Chen SD. Microglia in the aging brain: relevance to neurodegeneration. Mol Neurodegener 2010; 5: 12
39. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005a; 65: 1863-72
40. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005b; 65: 1863-72
41. Mollenhauer B, Cepek L, Bibl M, Wiltfang J, Schulz-Schaeffer WJ, Ciesielczyk B, et al. 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
42. 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
43. 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
44. Mollenhauer B, Schlossmacher MG. CSF synuclein: adding to the biomarker footprint of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2010; 81: 590-1
45. Mollenhauer B, Trautmann E, Otte B, Ng J, Spreer A, Lange P, et al. alpha-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system. J Neural Transm 2012; 119: 739-46
46. Mollenhauer B, Trautmann E, Sixel-Doring F, Wicke T, Ebentheuer J, Schaumburg M, et al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 2013a; 81: 1226-34
47. Mollenhauer B, Trautmann E, Taylor P, Manninger P, Sixel-Doring F, Ebentheuer J, et al. Total CSF alpha-synuclein is lower in de novo Parkinson patients than in healthy subjects. Neurosci Lett 2013b; 532: 44-8
48. Montine TJ, Shi M, Quinn JF, Peskind ER, Craft S, Ginghina C, et al. CSF Abeta and tau in Parkinson's disease with cognitive impairment. Mov Disord 2010; 25: 2682-5
49. Mougenot AL, Nicot S, Bencsik A, Morignat E, Verchere J, Lakhdar L, et al. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 2012; 33: 2225-8
50. 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
51. 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
52. Noguchi-Shinohara M, Tokuda T, Yoshita M, Kasai T, Ono K, Nakagawa M, et al. CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer's disease. Brain Res 2009; 1251: 1-6
53. 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
54. Ohrfelt A, Grognet P, Andreasen N, Wallin A, Vanmechelen E, Blennow K, et al. Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett 2009; 450: 332-5
55. Oosthuyzen W, Sime NE, Ivy JR, Turtle EJ, Street JM, Pound J, et al. Quantification of human urinary exosomes by nanoparticle tracking analysis. J Physiol 2013; 591(Pt 23): 5833-42
56. Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, et al. Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One 2008; 3: e1867
57. Popescu BO, Toescu EC, Popescu LM, Bajenaru O, Muresanu DF, Schultzberg M, et al. Blood-brain barrier alterations in ageing and dementia. J Neurol Sci 2009; 283: 99-106
58. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson's disease: a systematic review and meta-analysis. Mov Disord 2014; 29: 1583-90
59. Reesink FE, Lemstra AW, van Dijk KD, Berendse HW, van de Berg WD, Klein M, et al. CSF alpha-synuclein does not discriminate dementia with Lewy bodies from Alzheimer's disease. J Alzheimers Dis 2010; 22: 87-95
60. Schneider A, Simons M. Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res 2013; 352: 33-47
61. Shi M, Liu C, Cook TJ, Bullock KM, Zhao Y, Ginghina C, et al. Plasma exosomal alpha-synuclein is likely CNS-derived and increased in Parkinson's disease. Acta Neuropathol 2014; 128: 639-50
62. Sokolova V, Ludwig AK, Hornung S, Rotan O, Horn PA, Epple M, et al. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces 2011; 87: 146-50
63. 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
64. Strauss K, Goebel C, Runz H, Mobius W, Weiss S, Feussner I, et al. Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann-Pick type C disease. J Biol Chem 2010; 285: 26279-88
65. Suzuki I, Noguchi M, Arito M, Sato T, Omoteyama K, Maedomari M, et al. Serum peptides as candidate biomarkers for dementia with Lewy bodies. Int J Geriatr Psychiatry 2015; 30: 1195-206
66. Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T, et al. Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010; 75: 1766-72
67. Tokuda T, Salem SA, Allsop D, Mizuno T, Nakagawa M, Qureshi MM, et al. Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. Biochem Biophys Res Commun 2006; 349: 162-6
68. Ulusoy A, Rusconi R, Perez-Revuelta BI, Musgrove RE, Helwig M, Winzen-Reichert B, et al. Caudo-rostral brain spreading of alphasynuclein through vagal connections. EMBO Mol Med 2013; 5: 1051-9
69. van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, et al. 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
70. 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
71. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011; 72: 57-71
72. Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, et al. 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.