{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:26:46Z","timestamp":1784244406894,"version":"3.55.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Diagn Ther"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1007\/s40291-020-00493-4","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T08:04:58Z","timestamp":1601021098000},"page":"703-713","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Potential of Liquid Biopsy of the Brain Using Blood Extracellular Vesicles: The First Step Toward Effective Neuroprotection Against Neurodegenerative Diseases"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-3037","authenticated-orcid":false,"given":"Hanin","family":"Abdel-Haq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,25]]},"reference":[{"key":"493_CR1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0140-6736(06)69113-7","volume":"368","author":"K Blennow","year":"2006","unstructured":"Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006;368:387\u2013403.","journal-title":"Lancet"},{"key":"493_CR2","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1016\/j.metabol.2014.10.030","volume":"64","author":"DB Miller","year":"2015","unstructured":"Miller DB, O'Callaghan JP. Biomarkers of Parkinson's disease: present and future. Metabolism. 2015;64:S40\u2013S46.","journal-title":"Metabolism"},{"key":"493_CR3","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1074\/mcp.R200007-MCP200","volume":"1","author":"NL Anderson","year":"2002","unstructured":"Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1:845\u201367.","journal-title":"Mol Cell Proteomics"},{"key":"493_CR4","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1021\/pr0500657","volume":"4","author":"JM Jacobs","year":"2005","unstructured":"Jacobs JM, Adkins JN, Qian WJ, Liu T, Shen Y, Camp DG 2nd, et al. Utilizing human blood plasma for proteomic biomarker discovery. J Proteome Res. 2005;4:1073\u201385.","journal-title":"J Proteome Res"},{"key":"493_CR5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jneuroim.2015.09.006","volume":"288","author":"C Porro","year":"2015","unstructured":"Porro C, Trotta T, Panaro MA. Microvesicles in the brain: Biomarker, messenger or mediator? J Neuroimmunol. 2015;288:70\u20138.","journal-title":"J Neuroimmunol"},{"key":"493_CR6","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1172\/JCI81129","volume":"126","author":"R Xu","year":"2016","unstructured":"Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ. Extracellular vesicle isolation and characterization: toward clinical application. J Clin Invest. 2016;126:1152\u201362.","journal-title":"J Clin Invest"},{"key":"493_CR7","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.bbadis.2015.09.020","volume":"1862","author":"KM Kanninen","year":"2016","unstructured":"Kanninen KM, Bister N, Koistinaho J, Malm T. Exosomes as new diagnostic tools in CNS diseases. Biochim Biophys Acta. 2016;1862:403\u201310.","journal-title":"Biochim Biophys Acta"},{"key":"493_CR8","doi-asserted-by":"crossref","first-page":"657086","DOI":"10.1155\/2015\/657086","volume":"2015","author":"J Lin","year":"2015","unstructured":"Lin J, Li J, Huang B, Liu J, Chen X, Chen XM, et al. Exosomes: novel biomarkers for clinical diagnosis. Sci World J. 2015;2015:657086.","journal-title":"Sci World J"},{"key":"493_CR9","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fnins.2017.00026","volume":"11","author":"FN Soria","year":"2017","unstructured":"Soria FN, Pampliega O, Bourdenx M, Meissner WG, Bezard E, Dehay B. Exosomes, an unmasked culprit in neurodegenerative diseases. Front Neurosci. 2017;11:26.","journal-title":"Front Neurosci"},{"key":"493_CR10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3402\/jev.v3.23743","volume":"3","author":"L Cheng","year":"2014","unstructured":"Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles. 2014;3:1\u201314.","journal-title":"J Extracell Vesicles"},{"key":"493_CR11","doi-asserted-by":"publisher","first-page":"e0183915","DOI":"10.1371\/journal.pone.0183915","volume":"12","author":"MR Fernando","year":"2017","unstructured":"Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL. New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS ONE. 2017;12:e0183915. https:\/\/doi.org\/10.1371\/journal.pone.0183915.","journal-title":"PLoS ONE"},{"key":"493_CR12","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fnins.2017.00278","volume":"11","author":"M Mustapic","year":"2017","unstructured":"Mustapic M, Eitan E, Werner JK Jr, Berkowitz ST, Lazaropoulos MP, Tran J, et al. Plasma extracellular vesicles enriched for neuronal origin: a potential window into brain pathologic processes. Front Neurosci. 2017;11:278.","journal-title":"Front Neurosci"},{"key":"493_CR13","first-page":"P281","volume":"10","author":"D Kapogiannis","year":"2014","unstructured":"Kapogiannis D, Fiandaca MS, Mapstone M, Boxer A, Eitan E, Schwartz JB, et al. Pathogenic proteins in neurally-derived blood exosomes as diagnostic and prognostic biomarkers for Alzheimer's disease. Alzheimer's Dementia. 2014;10:P281.","journal-title":"Alzheimer's Dementia"},{"issue":"600\u20137","key":"493_CR14","first-page":"e1","volume":"11","author":"MS Fiandaca","year":"2015","unstructured":"Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, et al. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study. Alzheimers Dement. 2015;11(600\u20137):e1.","journal-title":"Alzheimers Dement"},{"key":"493_CR15","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1096\/fj.14-262048","volume":"29","author":"D Kapogiannis","year":"2015","unstructured":"Kapogiannis D, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, et al. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease. FASEB J. 2015;29:589\u201396.","journal-title":"FASEB J"},{"key":"493_CR16","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nm1286","volume":"11","author":"J Castilla","year":"2005","unstructured":"Castilla J, Sa\u00e1 P, Soto C. Detection of prions in blood. Nat Med. 2005;11:982\u20135.","journal-title":"Nat Med"},{"key":"493_CR17","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1099\/vir.0.000117","volume":"96","author":"F Properzi","year":"2015","unstructured":"Properzi F, Logozzi M, Abdel-Haq H, Federici C, Lugini L, Azzarito T, et al. Detection of exosomal prions in blood by immunochemistry techniques. J Gen Virol. 2015;96:1969\u201374.","journal-title":"J Gen Virol"},{"key":"493_CR18","doi-asserted-by":"crossref","first-page":"29247","DOI":"10.1074\/jbc.M114.589564","volume":"289","author":"P Sa\u00e1","year":"2014","unstructured":"Sa\u00e1 P, Yakovleva O, de Castro J, Vasilyeva I, De Paoli SH, Simak J, et al. First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification. J Biol Chem. 2014;289:29247\u201360.","journal-title":"J Biol Chem"},{"key":"493_CR19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.transci.2016.07.013","volume":"55","author":"L Cervenakova","year":"2016","unstructured":"Cervenakova L, Sa\u00e1 P, Yakovleva O, Vasilyeva I, de Castro J, Brown P, et al. Are prions transported by plasma exosomes? Transfus Apher Sci. 2016;55:70\u201383.","journal-title":"Transfus Apher Sci"},{"key":"493_CR20","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.bbrc.2016.09.090","volume":"483","author":"C Quek","year":"2017","unstructured":"Quek C, Hill AF. The role of extracellular vesicles in neurodegenerative diseases. Biochem Biophys Res Commun. 2017;483:1178\u201386.","journal-title":"Biochem Biophys Res Commun"},{"key":"493_CR21","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3390\/ijms19030663","volume":"19","author":"FX Guix","year":"2018","unstructured":"Guix FX, Corbett GT, Cha DJ, Mustapic M, Liu W, Mengel D, et al. Detection of aggregation-competent tau in neuron-derived extracellular vesicles. Int J Mol Sci. 2018;19:663.","journal-title":"Int J Mol Sci"},{"key":"493_CR22","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/acn3.211","volume":"2","author":"EJ Goetzl","year":"2015","unstructured":"Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, et al. Low neural exosomal levels of cellular survival factors in Alzheimer's disease. Ann Clin Transl Neurol. 2015;2:769\u201373.","journal-title":"Ann Clin Transl Neurol"},{"key":"493_CR23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1212\/WNL.0000000000001702","volume":"85","author":"EJ Goetzl","year":"2015","unstructured":"Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, et al. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 2015;85:40\u20137.","journal-title":"Neurology"},{"key":"493_CR24","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1096\/fj.201600816R","volume":"30","author":"EJ Goetzl","year":"2016","unstructured":"Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease. FASEB J. 2016;30:4141\u20138.","journal-title":"FASEB J"},{"key":"493_CR25","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1096\/fj.201700731R","volume":"32","author":"EJ Goetzl","year":"2018","unstructured":"Goetzl EJ, Abner EL, Jicha GA, Kapogiannis D, Schwartz JB. Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease. FASEB J. 2018;32:888\u201393.","journal-title":"FASEB J"},{"key":"493_CR26","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00401-014-1314-y","volume":"28","author":"M Shi","year":"2014","unstructured":"Shi M, Liu C, Cook TJ, Bullock KM, Zhao Y, Ginghina C, et al. Plasma exosomal \u03b1-synuclein is likely CNS-derived and increased in Parkinson's disease. Acta Neuropathol. 2014;28:639\u201350.","journal-title":"Acta Neuropathol"},{"key":"493_CR27","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3389\/fncel.2018.00125","volume":"12","author":"S Cerri","year":"2018","unstructured":"Cerri S, Ghezzi C, Sampieri M, Siani F, Avenali M, Dornini G, et al. The exosomal\/total \u03b1-synuclein ratio in plasma is associated with glucocerebrosidase activity and correlates with measures of disease severity in PD patients. Front Cell Neurosci. 2018;12:125.","journal-title":"Front Cell Neurosci"},{"key":"493_CR28","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3389\/fnagi.2018.00438","volume":"10","author":"ZH Zhao","year":"2019","unstructured":"Zhao ZH, Chen ZT, Zhou RL, Zhang X, Ye QY, Wang YZ. Increased DJ-1 and \u03b1-synuclein in plasma neural-derived exosomes as potential markers for Parkinson's Disease. Front Aging Neurosci. 2019;10:438.","journal-title":"Front Aging Neurosci"},{"key":"493_CR29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/acn3.175","volume":"2","author":"PR Tomlinson","year":"2015","unstructured":"Tomlinson PR, Zheng Y, Fischer R, Heidasch R, Gardiner C, Evetts S, et al. Identification of distinct circulating exosomes in Parkinson's disease. Ann Clin Transl Neurol. 2015;2:353\u201361.","journal-title":"Ann Clin Transl Neurol"},{"key":"493_CR30","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jalz.2016.08.012","volume":"13","author":"ED Hamlett","year":"2017","unstructured":"Hamlett ED, Goetzl EJ, Ledreux A, Vasilevko V, Boger HA, LaRosa A, et al. Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome. Alzheimers Dement. 2017;13:541\u20139.","journal-title":"Alzheimers Dement"},{"key":"493_CR31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.neurobiolaging.2008.04.002","volume":"31","author":"AM Moloney","year":"2010","unstructured":"Moloney AM, Griffin RJ, Timmons S, O'Connor R, Ravid R, O'Neill C. Defects in IGF-1 receptor, insulin receptor and IRS-1\/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging. 2010;31:224\u201343.","journal-title":"Neurobiol Aging"},{"key":"493_CR32","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","volume":"122","author":"K Talbot","year":"2012","unstructured":"Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, et al. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest. 2012;122:1316\u201338.","journal-title":"J Clin Invest"},{"key":"493_CR33","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.mcn.2005.12.003","volume":"31","author":"J Faur\u00e9","year":"2006","unstructured":"Faur\u00e9 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\u20138.","journal-title":"Mol Cell Neurosci"},{"key":"493_CR34","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/sj.ki.5002640","volume":"73","author":"Y Allory","year":"2008","unstructured":"Allory Y, Audard V, Fontanges P, Ronco P, Debiec H. The L1 cell adhesion molecule is the L1 cell adhesion molecule is a potential biomarker of human distal nephron injury in acute tubular necrosis. Kidney Int. 2008;73:751\u20138.","journal-title":"Kidney Int"},{"key":"493_CR35","doi-asserted-by":"crossref","first-page":"55276","DOI":"10.18632\/oncotarget.10527","volume":"7","author":"S Inaguma","year":"2016","unstructured":"Inaguma S, Wang Z, Lasota JP, Miettinen MM. Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors: an immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors. Oncotarget. 2016;7:55276\u201389.","journal-title":"Oncotarget"},{"key":"493_CR36","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2462","author":"D Kapogiannis","year":"2019","unstructured":"Kapogiannis D, Mustapic M, Shardell MD, Berkowitz ST, Diehl TC, Spangler RD, et al. Association of extracellular vesicle biomarkers with alzheimer disease in the baltimore longitudinal study of aging. JAMA Neurol. 2019. https:\/\/doi.org\/10.1001\/jamaneurol.2019.2462.","journal-title":"JAMA Neurol"},{"key":"493_CR37","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dadm.2016.04.001","volume":"3","author":"CN Winston","year":"2016","unstructured":"Winston CN, Goetzl EJ, Akers JC, Carter BS, Rockenstein EM, Galasko D, et al. Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst). 2016;3:63\u201372.","journal-title":"Alzheimers Dement (Amst)"},{"key":"493_CR38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.dadm.2018.11.002","volume":"11","author":"CN Winston","year":"2019","unstructured":"Winston CN, Goetzl EJ, Schwartz JB, Elahi FM, Rissman RA. Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia. Alzheimers Dement (Amst). 2019;11:61\u20136.","journal-title":"Alzheimers Dement (Amst)"},{"key":"493_CR39","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4103\/1673-5374.243709","volume":"14","author":"H Abdel-Haq","year":"2019","unstructured":"Abdel-Haq H. Blood exosomes as a tool for monitoring treatment efficacy and progression of neurodegenerative diseases. Neural Regen Res. 2019;14:72\u20134.","journal-title":"Neural Regen Res"},{"key":"493_CR40","first-page":"327","volume":"17","author":"B Ridolfi","year":"2017","unstructured":"Ridolfi B, Abdel-Haq H. Neurodegenerative disorders treatment: the MicroRNA role. Curr Gene Ther. 2017;17:327\u201363.","journal-title":"Curr Gene Ther"},{"key":"493_CR41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2015.02.019","volume":"87","author":"DD Taylor","year":"2015","unstructured":"Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods. 2015;87:3\u201310.","journal-title":"Methods"},{"key":"493_CR42","doi-asserted-by":"crossref","first-page":"119","DOI":"10.6065\/apem.2016.21.3.119","volume":"21","author":"MJ Lee","year":"2016","unstructured":"Lee MJ, Park DH, Kang JH. Exosomes as the source of biomarkers of metabolic diseases. Ann Pediatr Endocrinol Metab. 2016;21:119\u201325.","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"493_CR43","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1016\/j.nano.2017.03.011","volume":"13","author":"EA Mol","year":"2017","unstructured":"Mol EA, Goumans MJ, Doevendans PA, Sluijter JPG, Vader P. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation. Nanomedicine. 2017;13:2061\u20135.","journal-title":"Nanomedicine"},{"key":"493_CR44","doi-asserted-by":"crossref","first-page":"1560809","DOI":"10.1080\/20013078.2018.1560809","volume":"8","author":"K Takov","year":"2018","unstructured":"Takov K, Yellon DM, Davidson SM. Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: yield, purity and functional potential. J Extracell Vesicles. 2018;8:1560809.","journal-title":"J Extracell Vesicles"},{"key":"493_CR45","doi-asserted-by":"crossref","unstructured":"Yuana Y, Levels J, Grootemaat A, Sturk A, Nieuwland R. Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation. J Extracell Vesicles. 2014;3:10.3402\/jev.v3.23262.","DOI":"10.3402\/jev.v3.23262"},{"key":"493_CR46","doi-asserted-by":"crossref","first-page":"24316","DOI":"10.1038\/srep24316","volume":"6","author":"BW S\u00f3dar","year":"2016","unstructured":"S\u00f3dar BW, Kittel \u00c1, P\u00e1l\u00f3czi K, Vukman KV, Osteikoetxea X, Szab\u00f3-Taylor K, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016;6:24316.","journal-title":"Sci Rep"},{"key":"493_CR47","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCRESAHA.117.311767","volume":"121","author":"JB Simonsen","year":"2017","unstructured":"Simonsen JB. What are we looking at? Extracellular vesicles, lipoproteins, or both? Circ Res. 2017;121:920\u20132.","journal-title":"Circ Res"},{"key":"493_CR48","doi-asserted-by":"crossref","first-page":"29509","DOI":"10.3402\/jev.v4.29509","volume":"4","author":"R Linares","year":"2015","unstructured":"Linares R, Tan S, Gounou C, Arraud N, Brisson AR. High-speed centrifugation induces aggregation of extracellular vesicles. J Extracell Vesicles. 2015;4:29509.","journal-title":"J Extracell Vesicles"},{"key":"493_CR49","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/pmic.201300282","volume":"13","author":"H Kalra","year":"2013","unstructured":"Kalra H, Adda CG, Liem M, Ang CS, Mechler A, Simpson RJ, et al. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics. 2013;13:3354\u201364.","journal-title":"Proteomics"},{"key":"493_CR50","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3389\/fphys.2018.01479","volume":"9","author":"Z On\u00f3di","year":"2018","unstructured":"On\u00f3di Z, Pelyhe C, Ter\u00e9zia Nagy C, Brenner GB, Alm\u00e1si L, Kittel \u00c1, et al. Isolation of high-purity extracellular vesicles by the combination of iodixanol density gradient ultracentrifugation and bind-elute chromatography from blood plasma. Front Physiol. 2018;9:1479.","journal-title":"Front Physiol"},{"key":"493_CR51","doi-asserted-by":"publisher","first-page":"1053282","DOI":"10.1155\/2019\/1053282","volume":"2019","author":"H Abdel-Haq","year":"2019","unstructured":"Abdel-Haq H. Analysis of the glycosylation profile of disease-associated water-soluble prion protein using lectins. Biomed Res Int. 2019;2019:1053282. https:\/\/doi.org\/10.1155\/2019\/1053282.","journal-title":"Biomed Res Int"},{"key":"493_CR52","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/acn3.309","volume":"3","author":"EL Abner","year":"2016","unstructured":"Abner EL, Jicha GA, Shaw LM, Trojanowski JQ, Goetzl EJ. Plasma neuronal exosomal levels of Alzheimer's disease biomarkers in normal aging. Ann Clin Transl Neurol. 2016;3:399\u2013403.","journal-title":"Ann Clin Transl Neurol"},{"key":"493_CR53","doi-asserted-by":"crossref","first-page":"5141","DOI":"10.1096\/fj.13-238980","volume":"27","author":"M Mitsuhashi","year":"2013","unstructured":"Mitsuhashi M, Taub DD, Kapogiannis D, Eitan E, Zukley L, Mattson MP, et al. Aging enhances release of exosomal cytokine mRNAs by A\u03b21-42-stimulated macrophages. FASEB J. 2013;27:5141\u201350.","journal-title":"FASEB J"},{"key":"493_CR54","doi-asserted-by":"crossref","first-page":"e1003002","DOI":"10.1371\/journal.ppat.1003002","volume":"8","author":"A Majer","year":"2012","unstructured":"Majer A, Medina SJ, Niu Y, Abrenica B, Manguiat KJ, Frost KL, et al. Early mechanisms of pathobiology are revealed by transcriptional temporal dynamics in hippocampal CA1 neurons of prion infected mice. PLoS Pathog. 2012;8:e1003002.","journal-title":"PLoS Pathog"},{"key":"493_CR55","doi-asserted-by":"crossref","first-page":"573784","DOI":"10.1155\/2015\/573784","volume":"2015","author":"S Berjaoui","year":"2015","unstructured":"Berjaoui S, Povedano M, Garcia-Esparcia P, Carmona M, Aso E, Ferrer I. Complex Inflammation mRNA-related response in ALS is region dependent. Neural Plast. 2015;2015:573784.","journal-title":"Neural Plast"},{"key":"493_CR56","doi-asserted-by":"crossref","unstructured":"Guedes JR, Cust\u00f3dia CM, Silva RJ, de Almeida LP, Pedroso de Lima MC, et al. Early miR-155 upregulation contributes to neuroinflammation in Alzheimer's disease triple transgenic mouse model. Hum Mol Genet. 2014;23:6286\u2013301.","DOI":"10.1093\/hmg\/ddu348"},{"key":"493_CR57","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3389\/fncel.2015.00426","volume":"9","author":"R von Bernhardi","year":"2015","unstructured":"von Bernhardi R, Cornejo F, Parada GE, Eugen\u00edn J. Role of TGF\u03b2 signaling in the pathogenesis of Alzheimer's disease. Front Cell Neurosci. 2015;9:426.","journal-title":"Front Cell Neurosci"},{"key":"493_CR58","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jalz.2019.05.002","volume":"15","author":"L Jia","year":"2019","unstructured":"Jia L, Qiu Q, Zhang H, Chu L, Du Y, Zhang J, et al. Concordance between the assessment of A\u03b242, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid. Alzheimers Dement. 2019;15:1071\u201380.","journal-title":"Alzheimers Dement"},{"key":"493_CR59","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.arcmed.2012.10.016","volume":"43","author":"RA Quintanilla","year":"2012","unstructured":"Quintanilla RA, Orellana JA, von Bernhardi R. Understanding risk factors for Alzheimer's disease: interplay of neuroinflammation, connexin-based communication and oxidative stress. Arch Med Res. 2012;43:632\u201344.","journal-title":"Arch Med Res"},{"key":"493_CR60","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.arr.2016.11.003","volume":"34","author":"MD Ikonomovic","year":"2017","unstructured":"Ikonomovic MD, Mi Z, Abrahamson EE. Disordered APP metabolism and neurovasculature in trauma and aging: combined risks for chronic neurodegenerative disorders. Ageing Res Rev. 2017;34:51\u201363.","journal-title":"Ageing Res Rev"},{"key":"493_CR61","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/cells9040851","volume":"9","author":"J Saint-Pol","year":"2020","unstructured":"Saint-Pol J, Gosselet F. Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells. 2020;9:851.","journal-title":"Cells"},{"key":"493_CR62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12987-018-0104-7","volume":"15","author":"SH Ramirez","year":"2018","unstructured":"Ramirez SH, Andrews AM, Paul D, Pachter JS. Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers. Fluids Barriers CNS. 2018;15:19.","journal-title":"Fluids Barriers CNS"},{"key":"493_CR63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","volume":"14","author":"M Sweeney","year":"2018","unstructured":"Sweeney M, Sagare A, Zlokovic B. Blood\u2013brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018;14:133\u201350.","journal-title":"Nat Rev Neurol"}],"container-title":["Molecular Diagnosis &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-020-00493-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40291-020-00493-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-020-00493-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T20:51:41Z","timestamp":1723668701000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40291-020-00493-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,25]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["493"],"URL":"https:\/\/doi.org\/10.1007\/s40291-020-00493-4","relation":{},"ISSN":["1177-1062","1179-2000"],"issn-type":[{"value":"1177-1062","type":"print"},{"value":"1179-2000","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,25]]},"assertion":[{"value":"2 September 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No financial support was received in relation to this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"H. Abdel-Haq has no conflicts of interest that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Research data have been provided in the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Materials"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent"}}]}}