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Cited by 181Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryCellular transport and secretion

New windows into the brain: Central nervous system-derived extracellular vesicles in blood

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Shi, Min, Sheng, Lifu, Stewart, Tessandra, Zabetian, Cyrus P., Zhang, Jing·2019·Progress in Neurobiology
DOI 10.1016/j.pneurobio.2019.01.005PMC PMC6546433
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Abstract

Extracellular vesicles (EVs), including exosomes and (shedding) microvesicles, are released by nearly all cell types and carry a cargo of proteins and nucleic acids that varies by the cell of origin. They are thought to play critical roles in normal central nervous system (CNS) function and neurological disorders. A recently revealed key characteristic of EVs is that they may travel between the CNS and peripheral circulation. This property has led to intense interest in how EVs might serve as a vehicle for toxic protein clearance and as a readily accessible source of biomarkers for CNS disorders. Furthermore, by bypassing the blood-brain barrier, modified EVs could serve as a unique drug delivery system that targets specific neuronal populations. Further work is necessary to develop and optimize techniques that enable high-yield capture of relevant EV populations, analyze individual EVs and their cargos, and validate preliminary results of EV-derived biomarkers in independent cohorts.

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Crossref · 10.1016/j.pneurobio.2019.01.005

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  • EVs have inherent targeting capabilities and can cross the BBB, facilitating efficient delivery of therapeutic cargo to the CNS.

    “In addition, EVs have inherent targeting capabilities and can cross the BBB, facilitating efficient delivery of therapeutic cargo to the CNS [54–57].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [54]

    The section on bi-directional transport reports that EVs can cross the BBB and that engineered EVs have delivered therapeutic cargo to brain cells in mice. It describes neuron targeting using EVs modified to express a targeting peptide, however, rather than establishing inherent targeting capability; it also frames therapeutic delivery as a potential application, not generally efficient delivery to the CNS. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Brain-derived EVs have the ability to penetrate the BBB and be released into peripheral circulation.

    “Brain-derived EVs have been found to harbor the ability to penetrate the BBB. This breakdown is crucial as it potentially allows for releasing these EVs into peripheral circulation [54–57].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [54]

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References 113 · Cited by 181

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  1. Abner EL, Jicha GA, Shaw LM, Trojanowski JQ and Goetzl EJ, 2016 Plasma neuronal exosomal levels of Alzheimer’s disease biomarkers in normal aging. Ann. Clin. Transl. Neurol 3, 399– 403. 27231710 PMC4863753
  2. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S and Wood MJ, 2011 Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol 29, 341– 345. 21423189
  3. Andaloussi SEL, Mager I, Breakefield XO and Wood MJ, 2013 Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov 12, 347– 357. 23584393
  4. Banks WA, Kovac A, Majerova P, Bullock KM, Shi M and Zhang J, 2017 Tau Proteins Cross the Blood-Brain Barrier. J. Alzheimers Dis 55, 411– 419. 27662303
  5. Bianco F, Perrotta C, Novellino L, Francolini M, Riganti L, Menna E, Saglietti L, Schuchman EH, Furlan R, Clementi E, Matteoli M and Verderio C, 2009 Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28, 1043– 1054. 19300439 PMC2664656
  6. Budnik V, Ruiz-Canada C and Wendler F, 2016 Extracellular vesicles round off communication in the nervous system. Nat. Rev. Neurosci 17, 160– 172. 26891626 PMC4989863
  7. Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G and Bonnerot C, 2005 Exosomal-like vesicles are present in human blood plasma. Int. Immunol 17, 879– 887. 15908444
  8. Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, Loguidice L, Soto H, Garrett M, Zhu LD, Sivaraman S, Chen C, Wong ET, Carter BS, Hochberg FH, Breakefield XO and Skog J, 2013 BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles. Mol. Ther. Nucleic Acids 2, e109. 23881452 PMC3732870
  9. Cheng L, Doecke JD, Sharples RA, Villemagne VL, Fowler CJ, Rembach A, Martins RN, Rowe CC, Macaulay SL, Masters CL and Hill AF, 2015 Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol. Psychiatry 20, 1188– 1196. 25349172
  10. Cooper JM, Wiklander PB, Nordin JZ, Al-Shawi R, Wood MJ, Vithlani M, Schapira AH, Simons JP, El-Andaloussi S and Alvarez-Erviti L, 2014 Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov. Disord 29, 1476– 1485. 25112864 PMC4204174
  11. Coumans FAW, Brisson AR, Buzas EI, Dignat-George F, Drees EEE, El-Andaloussi S, Emanueli C, Gasecka A, Hendrix A, Hill AF, Lacroix R, Lee Y, van Leeuwen TG, Mackman N, Mager I, Nolan JP, van der Pol E, Pegtel DM, Sahoo S, Siljander PRM, Sturk G, de Wever O and Nieuwland R, 2017 Methodological Guidelines to Study Extracellular Vesicles. Circ. Res 120, 1632– 1648. 28495994
  12. Dinkins MB, Dasgupta S, Wang G, Zhu G and Bieberich E, 2014 Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol. Aging 35, 1792– 1800. 24650793 PMC4035236
  13. Dragovic RA, Gardiner C, Brooks AS, Tannetta DS, Ferguson DJ, Hole P, Carr B, Redman CW, Harris AL, Dobson PJ, Harrison P and Sargent IL, 2011 Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine 7, 780– 788. 21601655 PMC3280380
  14. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H and Raposo G, 2004 Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. U. S. A 101, 9683– 9688. 15210972 PMC470735
  15. Garcia-Romero N, Carrion-Navarro J, Esteban-Rubio S, Lazaro-Ibanez E, Peris-Celda M, Alonso MM, Guzman-De-Villoria J, Fernandez-Carballal C, de Mendivil AO, Garcia-Duque S, Escobedo-Lucea C, Prat-Acin R, Belda-Iniesta C and Ayuso-Sacido A, 2017 DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients. Oncotarget 8, 1416– 1428. 27902458 PMC5352065
  16. George JN, Thoi LL, McManus LM and Reimann TA, 1982 Isolation of human platelet membrane microparticles from plasma and serum. Blood 60, 834– 840. 7115953
  17. Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, Carlson OD, Mustapic M and Kapogiannis D, 2015a Low neural exosomal levels of cellular survival factors in Alzheimer’s disease. Ann. Clin. Transl. Neurol 2, 769– 773. 26273689 PMC4531059
  18. Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL and Kapogiannis D, 2015b Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 85, 40– 47. 26062630 PMC4501943
  19. Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, Jicha GA, Karydas AM, Boxer A and Miller BL, 2016a Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 30, 4141– 4148. 27601437 PMC5102122
  20. Goetzl EJ, Mustapic M, Kapogiannis D, Eitan E, Lobach IV, Goetzl L, Schwartz JB and Miller BL, 2016b Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease. FASEB J 30, 3853– 3859. 27511944 PMC5067254
  21. Goetzl EJ, Schwartz JB, Abner EL, Jicha GA and Kapogiannis D, 2018b High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann. Neurol 83, 544– 552. 29406582 PMC5867263
  22. Goetzl L, Darbinian N and Goetzl EJ, 2016c Novel window on early human neurodevelopment via fetal exosomes in maternal blood. Ann. Clin. Transl. Neurol 3, 381– 385. 27231707 PMC4863750
  23. Gomes C, Keller S, Altevogt P and Costa J, 2007 Evidence for secretion of Cu,Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis. Neurosci. Lett 428, 43– 46. 17942226
  24. Gould SJ and Raposo G, 2013 As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles 2, DOI: 10.3402/jev.v3402i3400.20389. PMC3760635 24009890 · DOI
  25. Grad LI, Yerbury JJ, Turner BJ, Guest WC, Pokrishevsky E, O’Neill MA, Yanai A, Silverman JM, Zeineddine R, Corcoran L, Kumita JR, Luheshi LM, Yousefi M, Coleman BM, Hill AF, Plotkin SS, Mackenzie IR and Cashman NR, 2014 Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. U. S. A 111, 3620– 3625. 24550511 PMC3948312
  26. Grey M, Dunning CJ, Gaspar R, Grey C, Brundin P, Sparr E and Linse S, 2015 Acceleration of alpha-synuclein aggregation by exosomes. J. Biol. Chem 290, 2969– 2982. 25425650 PMC4317028
  27. Guix FX, Corbett GT, Cha DJ, Mustapic M, Liu W, Mengel D, Chen Z, Aikawa E, Young-Pearse T, Kapogiannis D, Selkoe DJ and Walsh DM, 2018 Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles. Int. J. Mol. Sci 19. PMC5877524 29495441
  28. Guo BB, Bellingham SA and Hill AF, 2016 Stimulating the Release of Exosomes Increases the Intercellular Transfer of Prions. J. Biol. Chem 291, 5128– 5137. 26769968 PMC4777847
  29. Han C, Sun X, Liu L, Jiang H, Shen Y, Xu X, Li J, Zhang G, Huang J, Lin Z, Xiong N and Wang T, 2016 Exosomes and Their Therapeutic Potentials of Stem Cells. Stem Cells Int 2016, 7653489. 26770213 PMC4684885
  30. Harding C, Heuser J and Stahl P, 1983 Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol 97, 329– 339. 6309857 PMC2112509
  31. Harrington MG, Fonteh AN, Oborina E, Liao P, Cowan RP, McComb G, Chavez JN, Rush J, Biringer RG and Huhmer AF, 2009 The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid. Cerebrospinal Fluid Res 6, 10. 19735572 PMC2746175
  32. Henriksen K, O’Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lonneborg A, Wyss-Coray T, Soares H, Bazenet C, Sjogren M, Hu W, Lovestone S, Karsdal MA and Weiner MW, 2014 The future of blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 10, 115– 131. 23850333 PMC4128378
  33. Howitt J and Hill AF, 2016 Exosomes in the Pathology of Neurodegenerative Diseases. J. Biol. Chem 291, 26589– 26597. 27852825 PMC5207170
  34. Huang JH, Yin XM, Xu Y, Xu CC, Lin X, Ye FB, Cao Y and Lin FY, 2017 Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Attenuates Apoptosis, Inflammation, and Promotes Angiogenesis after Spinal Cord Injury in Rats. J. Neurotrauma 34, 3388– 3396. 28665182
  35. Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R and Lee H, 2014 Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat. Biotechnol 32, 490– 495. 24752081 PMC4356947
  36. Kanwar SS, Dunlay CJ, Simeone DM and Nagrath S, 2014 Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab. Chip 14, 1891– 1900. 24722878 PMC4134440
  37. Kapogiannis D, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, Frassetto L, Petersen RC, Miller BL and Goetzl EJ, 2015 Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer’s disease. FASEB J 29, 589– 596. 25342129 PMC4314222
  38. Kenwrick S, Watkins A and De Angelis E, 2000 Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum. Mol. Genet 9, 879– 886. 10767310
  39. Kibria G, Ramos EK, Lee KE, Bedoyan S, Huang S, Samaeekia R, Athman JJ, Harding CV, Lotvall J, Harris L, Thompson CL and Liu H, 2016 A rapid, automated surface protein profiling of single circulating exosomes in human blood. Sci. Rep 6, 36502. 27819324 PMC5098148
  40. Kojima R, Bojar D, Rizzi G, Hamri GC, El-Baba MD, Saxena P, Auslander S, Tan KR and Fussenegger M, 2018 Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat. Commun 9, 1305. 29610454 PMC5880805
  41. Kramer-Albers EM, Bretz N, Tenzer S, Winterstein C, Mobius W, Berger H, Nave KA, Schild H and Trotter J, 2007 Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin. Appl 1, 1446– 1461. 21136642
  42. Lachenal G, Pernet-Gallay K, Chivet M, Hemming FJ, Belly A, Bodon G, Blot B, Haase G, Goldberg Y and Sadoul R, 2011 Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol. Cell. Neurosci 46, 409– 418. 21111824
  43. Lee HK, Finniss S, Cazacu S, Xiang C and Brodie C, 2014 Mesenchymal stem cells deliver exogenous miRNAs to neural cells and induce their differentiation and glutamate transporter expression. Stem Cells Dev 23, 2851– 2861. 25036385
  44. Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B and Rak J, 2011 Microvesicles as mediators of intercellular communication in cancer--the emerging science of cellular ‘debris’. Semin. Immunopathol 33, 455– 467. 21318413
  45. Lener T, Gimona M, Aigner L, Borger V, Buzas E, Camussi G, Chaput N, Chatterjee D, Court FA, Del Portillo HA, O’Driscoll L, Fais S, Falcon-Perez JM, Felderhoff-Mueser U, Fraile L, Gho YS, Gorgens A, Gupta RC, Hendrix A, Hermann DM, Hill AF, Hochberg F, Horn PA, de Kleijn D, Kordelas L, Kramer BW, Kramer-Albers EM, Laner-Plamberger S, Laitinen S, Leonardi T, Lorenowicz MJ, Lim SK, Lotvall J, Maguire CA, Marcilla A, Nazarenko I, Ochiya T, Patel T, Pedersen S, Pocsfalvi G, Pluchino S, Quesenberry P, Reischl IG, Rivera FJ, Sanzenbacher R, Schallmoser K, Slaper-Cortenbach I, Strunk D, Tonn T, Vader P, van Balkom BW, Wauben M, Andaloussi SE, Thery C, Rohde E and Giebel B, 2015 Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J. Extracell. Vesicles 4, 30087. 26725829 PMC4698466
  46. Lleo A, Cavedo E, Parnetti L, Vanderstichele H, Herukka SK, Andreasen N, Ghidoni R, Lewczuk P, Jeromin A, Winblad B, Tsolaki M, Mroczko B, Visser PJ, Santana I, Svenningsson P, Blennow K, Aarsland D, Molinuevo JL, Zetterberg H and Mollenhauer B, 2015 Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases. Nat. Rev. Neurol 11, 41– 55. 25511894
  47. Lotvall J, Hill AF, Hochberg F, Buzas EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, Sahoo S, Tahara H, Wauben MH, Witwer KW and Thery C, 2014 Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 3, 26913. 25536934 PMC4275645
  48. Lugli G, Cohen AM, Bennett DA, Shah RC, Fields CJ, Hernandez AG and Smalheiser NR, 2015 Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers. PLoS ONE 10, e0139233. 26426747 PMC4591334
  49. Mateescu B, Kowal EJ, van Balkom BW, Bartel S, Bhattacharyya SN, Buzas EI, Buck AH, de Candia P, Chow FW, Das S, Driedonks TA, Fernandez-Messina L, Haderk F, Hill AF, Jones JC, Van Keuren-Jensen KR, Lai CP, Lasser C, Liegro ID, Lunavat TR, Lorenowicz MJ, Maas SL, Mager I, Mittelbrunn M, Momma S, Mukherjee K, Nawaz M, Pegtel DM, Pfaffl MW, Schiffelers RM, Tahara H, Thery C, Tosar JP, Wauben MH, Witwer KW and Nolte-’t Hoen EN, 2017 Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper. J. Extracell. Vesicles 6, 1286095. 28326170 PMC5345583
  50. Matsumoto J, Stewart T, Sheng L, Li N, Bullock K, Song N, Shi M, Banks WA and Zhang J, 2017 Transmission of alpha-synuclein-containing erythrocyte-derived extracellular vesicles across the blood-brain barrier via adsorptive mediated transcytosis: another mechanism for initiation and progression of Parkinson’s disease? Acta Neuropathol. Commun 5, 71. 28903781 PMC5598000
  51. Medina M and Avila J, 2014 The role of extracellular Tau in the spreading of neurofibrillary pathology. Front. Cell. Neurosci 8, 113. 24795568 PMC4005959
  52. Minciacchi VR, Zijlstra A, Rubin MA and Di Vizio D, 2017 Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed? Prostate Cancer Prostatic Dis 20, 251– 258. 28374743 PMC5569339
  53. Mora EM, Alvarez-Cubela S and Oltra E, 2015 Biobanking of Exosomes in the Era of Precision Medicine: Are We There Yet? Int. J. Mol. Sci 17. PMC4730260 26712742
  54. Mullins RJ, Mustapic M, Goetzl EJ and Kapogiannis D, 2017 Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer’s disease. Hum. Brain Mapp 38, 1933– 1940. 28105773 PMC5342917
  55. Mustapic M, Eitan E, Werner JK Jr., Berkowitz ST, Lazaropoulos MP, Tran J, Goetzl EJ and Kapogiannis D, 2017 Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes. Front. Neurosci 11, 278. 28588440 PMC5439289
  56. Ngolab J, Trinh I, Rockenstein E, Mante M, Florio J, Trejo M, Masliah D, Adame A, Masliah E and Rissman RA, 2017 Brain-derived exosomes from dementia with Lewy bodies propagate alpha-synuclein pathology. Acta Neuropathol. Commun 5, 46. 28599681 PMC5466770
  57. Pan BT and Johnstone RM, 1983 Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33, 967– 978. 6307529
  58. Pan BT, Teng K, Wu C, Adam M and Johnstone RM, 1985 Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol 101, 942– 948. 2993317 PMC2113705
  59. Polanco JC, Scicluna BJ, Hill AF and Gotz J, 2016 Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner. J. Biol. Chem 291, 12445– 12466. 27030011 PMC4933440
  60. Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P and Simons K, 2006 Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. U. S. A 103, 11172– 11177. 16837572 PMC1544060
  61. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P and Ratajczak MZ, 2006 Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20, 847– 856. 16453000
  62. Record M, Subra C, Silvente-Poirot S and Poirot M, 2011 Exosomes as intercellular signalosomes and pharmacological effectors. Biochem. Pharmacol 81, 1171– 1182. 21371441
  63. Ridder K, Keller S, Dams M, Rupp AK, Schlaudraff J, Del Turco D, Starmann J, Macas J, Karpova D, Devraj K, Depboylu C, Landfried B, Arnold B, Plate KH, Hoglinger G, Sultmann H, Altevogt P and Momma S, 2014 Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol 12, e1001874. 24893313 PMC4043485
  64. Rissin DM, Fournier DR, Piech T, Kan CW, Campbell TG, Song L, Chang L, Rivnak AJ, Patel PP, Provuncher GK, Ferrell EP, Howes SC, Pink BA, Minnehan KA, Wilson DH and Duffy DC, 2011 Simultaneous detection of single molecules and singulated ensembles of molecules enables immunoassays with broad dynamic range. Anal. Chem 83, 2279– 2285. 21344864 PMC3056883
  65. Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, Piech T, Patel PP, Chang L, Rivnak AJ, Ferrell EP, Randall JD, Provuncher GK, Walt DR and Duffy DC, 2010 Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat. Biotechnol 28, 595– 599. 20495550 PMC2919230
  66. Rose JA, Wanner N, Cheong HI, Queisser K, Barrett P, Park M, Hite C, Naga Prasad SV, Erzurum S and Asosingh K, 2016 Flow Cytometric Quantification of Peripheral Blood Cell beta-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension. PLoS ONE 11, e0156940. 27270458 PMC4896479
  67. Shao H, Chung J, Balaj L, Charest A, Bigner DD, Carter BS, Hochberg FH, Breakefield XO, Weissleder R and Lee H, 2012 Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat. Med 18, 1835– 1840. 23142818 PMC3518564
  68. Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, Hochberg FH, Breakefield XO, Lee H and Weissleder R, 2015 Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat. Commun 6, 6999. 25959588 PMC4430127
  69. Shi M, Liu C, Cook TJ, Bullock KM, Zhao Y, Ginghina C, Li Y, Aro P, Dator R, He C, Hipp MJ, Zabetian CP, Peskind ER, Hu SC, Quinn JF, Galasko DR, Banks WA and Zhang J, 2014 Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson’s disease. Acta Neuropathol 128, 639– 650. 24997849 PMC4201967
  70. Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Kruger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, Steffens M, Okun MS, Racette BA, Cookson MR, Foote KD, Fernandez HH, Traynor BJ, Schreiber S, Arepalli S, Zonozi R, Gwinn K, van der Brug M, Lopez G, Chanock SJ, Schatzkin A, Park Y, Hollenbeck A, Gao J, Huang X, Wood NW, Lorenz D, Deuschl G, Chen H, Riess O, Hardy JA, Singleton AB and Gasser T, 2009 Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat. Genet 41, 1308– 1312. 19915575 PMC2787725
  71. Simon D, Garcia-Garcia E, Gomez-Ramos A, Falcon-Perez JM, Diaz-Hernandez M, Hernandez F and Avila J, 2012 Tau overexpression results in its secretion via membrane vesicles. Neurodegener. Dis 10, 73– 75. 22269430
  72. Simpson RJ, Kalra H and Mathivanan S, 2012 ExoCarta as a resource for exosomal research. J. Extracell. Vesicles 1, 18374. PMC3760644 24009883
  73. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr., Carter BS, Krichevsky AM and Breakefield XO, 2008 Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol 10, 1470– 1476. 19011622 PMC3423894
  74. Sodar BW, Kittel A, Paloczi K, Vukman KV, Osteikoetxea X, Szabo-Taylor K, Nemeth A, Sperlagh B, Baranyai T, Giricz Z, Wiener Z, Turiak L, Drahos L, Pallinger E, Vekey K, Ferdinandy P, Falus A and Buzas EI, 2016 Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci. Rep 6, 24316. 27087061 PMC4834552
  75. Sterzenbach U, Putz U, Low LH, Silke J, Tan SS and Howitt J, 2017 Engineered Exosomes as Vehicles for Biologically Active Proteins. Mol. Ther 25, 1269– 1278. 28412169 PMC5474961
  76. Street JM, Barran PE, Mackay CL, Weidt S, Balmforth C, Walsh TS, Chalmers RT, Webb DJ and Dear JW, 2012 Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J. Transl. Med 10, 5. 22221959 PMC3275480
  77. Stuendl A, Kunadt M, Kruse N, Bartels C, Moebius W, Danzer KM, Mollenhauer B and Schneider A, 2016 Induction of alpha-synuclein aggregate formation by CSF exosomes from patients with Parkinson’s disease and dementia with Lewy bodies. Brain 139, 481– 494. 26647156 PMC4805087
  78. Suire CN, Eitan E, Shaffer NC, Tian Q, Studenski S, Mattson MP and Kapogiannis D, 2017 Walking speed decline in older adults is associated with elevated pro-BDNF in plasma extracellular vesicles. Exp. Gerontol 98, 209– 216. 28843509 PMC5642035
  79. Sun B, Dalvi P, Abadjian L, Tang N and Pulliam L, 2017 Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV. AIDS 31, F9– f17. 28692534 PMC5578870
  80. Thomas B and Beal MF, 2007 Parkinson’s disease. Hum. Mol. Genet 16 Spec No. 2, R183– 194. 17911161
  81. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ and Lotvall JO, 2007 Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol 9, 654– 659. 17486113
  82. Van Deun J, Mestdagh P, Sormunen R, Cocquyt V, Vermaelen K, Vandesompele J, Bracke M, De Wever O and Hendrix A, 2014 The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J. Extracell. Vesicles 3. PMC4169610 25317274
  83. Vella LJ, Greenwood DL, Cappai R, Scheerlinck JP and Hill AF, 2008 Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid. Vet. Immunol. Immunopathol 124, 385– 393. 18501435
  84. Vella LJ, Sharples RA, Lawson VA, Masters CL, Cappai R and Hill AF, 2007 Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J. Pathol 211, 582– 590. 17334982
  85. Weng Y, Sui Z, Shan Y, Hu Y, Chen Y, Zhang L and Zhang Y, 2016 Effective isolation of exosomes with polyethylene glycol from cell culture supernatant for in-depth proteome profiling. Analyst 141, 4640– 4646. 27229443
  86. Winston CN, Goetzl EJ, Akers JC, Carter BS, Rockenstein EM, Galasko D, Masliah E and Rissman RA, 2016 Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst) 3, 63– 72. 27408937 PMC4925777
  87. Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG and Chopp M, 2013 Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J. Cereb. Blood Flow Metab 33, 1711– 1715. 23963371 PMC3824189
  88. Xu R, Greening DW, Zhu HJ, Takahashi N and Simpson RJ, 2016 Extracellular vesicle isolation and characterization: toward clinical application. J. Clin. Invest 126, 1152– 1162. 27035807 PMC4811150
  89. Xu R, Rai A, Chen M, Suwakulsiri W, Greening DW and Simpson RJ, 2018 Extracellular vesicles in cancer - implications for future improvements in cancer care. Nature reviews. Clinical oncology 15, 617– 638. 29795272
  90. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Kramer-Albers EM, Laitinen S, Lasser C, Lener T, Ligeti E, Line A, Lipps G, Llorente A, Lotvall J, Mancek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-’t Hoen EN, Nyman TA, O’Driscoll L, Olivan M, Oliveira C, Pallinger E, Del Portillo HA, Reventos J, Rigau M, Rohde E, Sammar M, Sanchez-Madrid F, Santarem N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH and De Wever O, 2015 Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4, 27066. 25979354 PMC4433489
  91. Yuyama K, Sun H, Mitsutake S and Igarashi Y, 2012 Sphingolipid-modulated exosome secretion promotes clearance of amyloid-beta by microglia. J. Biol. Chem 287, 10977– 10989. 22303002 PMC3322859
  92. Yuyama K, Sun H, Sakai S, Mitsutake S, Okada M, Tahara H, Furukawa J, Fujitani N, Shinohara Y and Igarashi Y, 2014 Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J. Biol. Chem 289, 24488– 24498. 25037226 PMC4148874
  93. Zabetian CP, Hutter CM, Factor SA, Nutt JG, Higgins DS, Griffith A, Roberts JW, Leis BC, Kay DM, Yearout D, Montimurro JS, Edwards KL, Samii A and Payami H, 2007 Association analysis of MAPT H1 haplotype and subhaplotypes in Parkinson’s disease. Ann. Neurol 62, 137– 144. 17514749 PMC2836920
  94. Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A and Xiong Y, 2015 Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J. Neurosurg 122, 856– 867. 25594326 PMC4382456
  95. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G and Amigorena S, 1998 Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med 4, 594– 600. 9585234

Authors
Shi, M., Sheng, L., Stewart, T., Zabetian, C. P., & Zhang, J.
Affiliations
University of Washington (US)
Corresponding author
Zhang, Jing
ORCID
Venue
Progress in Neurobiology
Publisher
Elsevier BV
Published
2019-04
Volume
175
Pages
96-106
ISSN
0301-0082 (ISSN-L)
DOI
10.1016/j.pneurobio.2019.01.005
PMC
PMC6546433
OpenAlex
W2914453053
Cited by
181
References
113
Citations by year
2026: 17 · 2025: 20 · 2024: 23 · 2023: 36 · 2022: 19 · 2021: 21 · 2020: 31 · 2019: 13 · 2013: 1
FWCI
1.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Progress in Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of HealthNational Institutes of Health (NIH) (U01 NS082137, U01 NS091272, R01 AG056711, R56 AG057417, R21 NS085425, P50 NS062684, R01 NS065070)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
extracellular vesicles, exosomes, microvesicles, central nervous system, blood-brain barrier, EV-based drug delivery, EV cargo
MeSH terms
Extracellular Vesicles, Animals, Brain, Central Nervous System, Humans

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