{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:05:55Z","timestamp":1787501155160,"version":"build-2736575974"},"reference-count":90,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["81430037"],"award-info":[{"award-number":["81430037"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFC1306300"],"award-info":[{"award-number":["2016YFC1306300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2018YFC1312001"],"award-info":[{"award-number":["2018YFC1312001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61633018 81801052"],"award-info":[{"award-number":["61633018 81801052"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M641414"],"award-info":[{"award-number":["2018M641414"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["Foundation2018M641414"],"award-info":[{"award-number":["Foundation2018M641414"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mechanisms of Ageing and Development"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.mad.2019.111175","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T18:50:53Z","timestamp":1572634253000},"page":"111175","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":49,"special_numbering":"C","title":["Extracellular vesicles as an emerging tool for the early detection of Alzheimer\u2019s disease"],"prefix":"10.1016","volume":"184","author":[{"given":"Tao-Ran","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ni","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic Zhen-Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mad.2019.111175_bib0005","series-title":"World Alzheimer Report 2018","author":"Patterson","year":"2018"},{"key":"10.1016\/j.mad.2019.111175_bib0010","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3389\/fnagi.2017.00356","article-title":"Perspective insights into disease progression, diagnostics, and therapeutic approaches in Alzheimer\u2019s disease: a judicious update","volume":"9","author":"Jan","year":"2017","journal-title":"Front Aging Neurosci."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0015","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.mcna.2013.01.002","article-title":"Clinical trials in predementia stages of Alzheimer disease","volume":"97","author":"Pillai","year":"2013","journal-title":"Med. Clin. North Am."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0020","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"issue":"9770","key":"10.1016\/j.mad.2019.111175_bib0025","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","article-title":"Alzheimer\u2019s disease","volume":"377","author":"Ballard","year":"2011","journal-title":"Lancet."},{"issue":"5","key":"10.1016\/j.mad.2019.111175_bib0030","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/ana.410270502","article-title":"Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: correlation with cognitive severity","volume":"27","author":"DeKosky","year":"1990","journal-title":"Ann Neurol."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0035","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1096\/fj.201700731R","article-title":"Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer\u2019s disease","volume":"32","author":"Goetzl","year":"2018","journal-title":"FASEB J."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0040","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/14737175.2016.1204234","article-title":"Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer\u2019s disease","volume":"17","author":"Lista","year":"2017","journal-title":"Expert Rev. Neurother."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0045","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmed.2007.12.002","article-title":"Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer\u2019s disease","volume":"14","author":"Reddy","year":"2008","journal-title":"Trends. Mol. Med."},{"issue":"8","key":"10.1016\/j.mad.2019.111175_bib0050","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a006361","article-title":"The ubiquitin-proteasome system and the autophagic-lysosomal system in Alzheimer disease","volume":"2","author":"Ihara","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.mad.2019.111175_bib0055","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1038\/ncomms11934","article-title":"Early role of vascular dysregulation on late-onset Alzheimer\u2019s disease based on multifactorial data-driven analysis","volume":"7","author":"Iturria-Medina","year":"2016","journal-title":"Nat. Commun."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0060","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0065","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.neurobiolaging.2008.04.002","article-title":"Defects in IGF-1 receptor, insulin receptor and IRS-1\/2 in Alzheimer\u2019s disease indicate possible resistance to IGF-1 and insulin signalling","volume":"31","author":"Moloney","year":"2010","journal-title":"Neurobiol Aging."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0070","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated brain insulin resistance in Alzheimer\u2019s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J. Clin. Invest."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0075","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00401-013-1157-y","article-title":"Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series","volume":"126","author":"Kovacs","year":"2013","journal-title":"Acta. Neuropathol."},{"issue":"9","key":"10.1016\/j.mad.2019.111175_bib0080","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13195-014-0082-1","article-title":"Prevalence of mixed pathologies in the aging brain","volume":"6","author":"Rahimi","year":"2014","journal-title":"Alzheimers Res. Ther."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0085","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jamaneurol.2014.4144","article-title":"Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density","volume":"72","author":"Curtis","year":"2015","journal-title":"JAMA Neurol."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0090","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S1474-4422(06)70355-6","article-title":"Association between CSF biomarkers and incipient Alzheimer\u2019s disease in patients with mild cognitive impairment: a follow-up study","volume":"5","author":"Hansson","year":"2006","journal-title":"Lancet Neurol."},{"issue":"6","key":"10.1016\/j.mad.2019.111175_bib0095","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/ana.23908","article-title":"Comparing positron emission tomography imaging and cerebrospinal fluid measurements of \u03b2-amyloid","volume":"74","author":"Landau","year":"2013","journal-title":"Ann. Neurol."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0100","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa1304839","article-title":"Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer\u2019s disease","volume":"370","author":"Salloway","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"9","key":"10.1016\/j.mad.2019.111175_bib0105","doi-asserted-by":"crossref","DOI":"10.3390\/ijms17091408","article-title":"Extracellular vesicles as New players in cellular senescence","volume":"17","author":"Urbanelli","year":"2016","journal-title":"Int. J. Mol. Sci."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0110","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.mad.2019.111175_bib0115","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jprot.2014.04.028","article-title":"Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset","volume":"106","author":"Chiasserini","year":"2014","journal-title":"J. Proteomics."},{"issue":"8","key":"10.1016\/j.mad.2019.111175_bib0120","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2217\/nnm.12.86","article-title":"Nanobiotechnology-based strategies for crossing the blood-brain barrier","volume":"7","author":"Jain","year":"2012","journal-title":"Nanomedicine (Lond)."},{"issue":"10","key":"10.1016\/j.mad.2019.111175_bib0125","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/mp.2014.127","article-title":"Prognostic serum miRNA biomarkers associated with Alzheimer\u2019s disease shows concordance with neuropsychological and neuroimaging assessment","volume":"20","author":"Cheng","year":"2015","journal-title":"Mol. Psychiatry."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0130","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.nantod.2015.04.004","article-title":"Cell-derived vesicles for drug therapy and diagnostics: opportunities and challenges","volume":"10","author":"Fuhrmann","year":"2015","journal-title":"Nano Today"},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0135","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/hbm.23494","article-title":"Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer\u2019s disease","volume":"38","author":"Mullins","year":"2017","journal-title":"Hum. Brain Mapp."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0140","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19030663","article-title":"Detection of aggregation-competent tau in neuron-derived extracellular vesicles","volume":"19","author":"Guix","year":"2018","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.mad.2019.111175_bib0145","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical Alzheimer\u2019s disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.mad.2019.111175_bib0150","doi-asserted-by":"crossref","DOI":"10.1001\/jamaneurol.2019.2462","article-title":"Association of extracellular vesicle biomarkers with Alzheimer disease in the baltimore longitudinal study of aging","author":"Kapogiannis","year":"2019","journal-title":"JAMA Neurol."},{"issue":"30","key":"10.1016\/j.mad.2019.111175_bib0155","doi-asserted-by":"crossref","first-page":"11172","DOI":"10.1073\/pnas.0603838103","article-title":"Alzheimer\u2019s disease beta-amyloid peptides are released in association with exosomes","volume":"103","author":"Rajendran","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"5","key":"10.1016\/j.mad.2019.111175_bib0160","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1096\/fj.07-9357com","article-title":"Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes","volume":"22","author":"Sharples","year":"2008","journal-title":"FASEB J."},{"issue":"25","key":"10.1016\/j.mad.2019.111175_bib0165","doi-asserted-by":"crossref","first-page":"18197","DOI":"10.1074\/jbc.M609475200","article-title":"Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies","volume":"282","author":"Vingtdeux","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"51","key":"10.1016\/j.mad.2019.111175_bib0170","doi-asserted-by":"crossref","first-page":"43108","DOI":"10.1074\/jbc.M112.404467","article-title":"The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space","volume":"287","author":"Perez-Gonzalez","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0175","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF02778005","article-title":"Induction of beta (A4)-amyloid in primates by injection of Alzheimer\u2019s disease brain homogenate. Comparison with transmission of spongiform encephalopathy","volume":"8","author":"Baker","year":"1994","journal-title":"Mol. Neurobiol."},{"issue":"6006","key":"10.1016\/j.mad.2019.111175_bib0180","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1126\/science.1194516","article-title":"Peripherally applied abeta-containing inoculates induce cerebral beta-amyloidosis","volume":"330","author":"Eisele","year":"2010","journal-title":"Science"},{"issue":"8","key":"10.1016\/j.mad.2019.111175_bib0185","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.neurobiolaging.2014.02.012","article-title":"Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer\u2019s disease","volume":"35","author":"Dinkins","year":"2014","journal-title":"Neurobiol. Aging."},{"issue":"33","key":"10.1016\/j.mad.2019.111175_bib0190","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1523\/JNEUROSCI.1429-16.2016","article-title":"Neutral sphingomyelinase-2 deficiency ameliorates Alzheimer\u2019s disease pathology and improves cognition in the 5XFAD mouse","volume":"36","author":"Dinkins","year":"2016","journal-title":"J. Neurosci."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0195","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00401-018-1868-1","article-title":"Alzheimer\u2019s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers","volume":"136","author":"Sardar","year":"2018","journal-title":"Acta. Neuropathol."},{"issue":"25","key":"10.1016\/j.mad.2019.111175_bib0200","doi-asserted-by":"crossref","first-page":"21384","DOI":"10.1074\/jbc.M112.340513","article-title":"Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD)","volume":"287","author":"Wang","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"14","key":"10.1016\/j.mad.2019.111175_bib0205","doi-asserted-by":"crossref","first-page":"10977","DOI":"10.1074\/jbc.M111.324616","article-title":"Sphingolipid-modulated exosome secretion promotes clearance of amyloid-\u03b2 by microglia","volume":"287","author":"Yuyama","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"35","key":"10.1016\/j.mad.2019.111175_bib0210","doi-asserted-by":"crossref","first-page":"24488","DOI":"10.1074\/jbc.M114.577213","article-title":"Decreased amyloid-\u03b2 pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice","volume":"289","author":"Yuyama","year":"2014","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0215","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.febslet.2014.11.027","article-title":"A potential function for neuronal exosomes: sequestering intracerebral amyloid-\u03b2 peptide","volume":"589","author":"Yuyama","year":"2015","journal-title":"FEBS Lett."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0220","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3233\/JAD-2010-1206","article-title":"Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading protease","volume":"19","author":"Bulloj","year":"2010","journal-title":"J. Alzheimers Dis."},{"issue":"48","key":"10.1016\/j.mad.2019.111175_bib0225","doi-asserted-by":"crossref","first-page":"37405","DOI":"10.1074\/jbc.M110.149468","article-title":"Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion","volume":"285","author":"Tamboli","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0230","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer\u2019s disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1995","journal-title":"Neurobiol. Aging."},{"issue":"20","key":"10.1016\/j.mad.2019.111175_bib0235","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1016\/j.febslet.2006.07.078","article-title":"Extracellular tau is toxic to neuronal cells","volume":"580","author":"G\u00f3mez-Ramos","year":"2006","journal-title":"FEBS Lett."},{"issue":"11","key":"10.1016\/j.mad.2019.111175_bib0240","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"issue":"6","key":"10.1016\/j.mad.2019.111175_bib0245","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1074\/jbc.M111.277061","article-title":"Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease","volume":"287","author":"Saman","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0250","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-016-0143-y","article-title":"The release and trans-synaptic transmission of tau via exosomes","volume":"12","author":"Wang","year":"2017","journal-title":"Mol Neurodegener."},{"issue":"1\u20134","key":"10.1016\/j.mad.2019.111175_bib0255","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000334915","article-title":"Tau overexpression results in its secretion via membrane vesicles","volume":"10","author":"Sim\u00f3n","year":"2012","journal-title":"Neurodegener Dis."},{"issue":"11","key":"10.1016\/j.mad.2019.111175_bib0260","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jalz.2016.04.003","article-title":"CNS tau efflux via exosomes is likely increased in Parkinson\u2019s disease but not in Alzheimer\u2019s disease","volume":"12","author":"Shi","year":"2016","journal-title":"Alzheimers Dement."},{"issue":"24","key":"10.1016\/j.mad.2019.111175_bib0265","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1074\/jbc.M115.709485","article-title":"Extracellular vesicles isolated from the brains of rTg4510 mice seed tau protein aggregation in a threshold-dependent manner","volume":"291","author":"Polanco","year":"2016","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0270","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40478-018-0514-4","article-title":"Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons","volume":"6","author":"Polanco","year":"2018","journal-title":"Acta. Neuropathol. Commun."},{"key":"10.1016\/j.mad.2019.111175_bib0275","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dadm.2016.04.001","article-title":"Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile","volume":"3","author":"Winston","year":"2016","journal-title":"Alzheimers Dement (Amst)."},{"issue":"11","key":"10.1016\/j.mad.2019.111175_bib0280","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1096\/fj.201600756R","article-title":"Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer\u2019s disease","volume":"30","author":"Goetzl","year":"2016","journal-title":"FASEB J."},{"issue":"8","key":"10.1016\/j.mad.2019.111175_bib0285","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jalz.2019.05.002","article-title":"Concordance between the assessment of A\u03b242, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid","volume":"15","author":"Jia","year":"2019","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.mad.2019.111175_bib0290","article-title":"Murphy MP. \u03b2-secretases, Alzheimer\u2019s disease, and down syndrome","volume":"2012","author":"Webb","year":"2012","journal-title":"Curr. Gerontol. Geriatr. Res."},{"issue":"5","key":"10.1016\/j.mad.2019.111175_bib0295","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jalz.2016.08.012","article-title":"Neuronal exosomes reveal Alzheimer\u2019s disease biomarkers in down syndrome","volume":"13","author":"Hamlett","year":"2017","journal-title":"Alzheimers Dement."},{"issue":"7","key":"10.1016\/j.mad.2019.111175_bib0300","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1097\/NEN.0000000000000207","article-title":"Cerebrospinal fluid particles in Alzheimer disease and Parkinson disease","volume":"74","author":"Yang","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"issue":"9","key":"10.1016\/j.mad.2019.111175_bib0305","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.bbadis.2016.06.001","article-title":"Are circulating microRNAs peripheral biomarkers for Alzheimer\u2019s disease","volume":"1862","author":"Kumar","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0310","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1515\/revneuro-2017-0042","article-title":"MicroRNA in Alzheimer\u2019s disease revisited: implications for major neuropathological mechanisms","volume":"29","author":"Dehghani","year":"2018","journal-title":"Rev. Neurosci."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0315","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2045-8118-10-4","article-title":"Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells","volume":"10","author":"Haqqani","year":"2013","journal-title":"Fluids Barriers CNS."},{"key":"10.1016\/j.mad.2019.111175_bib0320","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-62703-453-1_3","article-title":"Methods of analysis of dendritic cell-derived exosome-shuttle microRNA and its horizontal propagation between dendritic cells","volume":"1024","author":"Montecalvo","year":"2013","journal-title":"Methods Mol. Biol."},{"issue":"10","key":"10.1016\/j.mad.2019.111175_bib0325","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139233","article-title":"Plasma exosomal miRNAs in persons with and without Alzheimer disease: altered expression and prospects for biomarkers","volume":"10","author":"Lugli","year":"2015","journal-title":"PLoS One"},{"issue":"5","key":"10.1016\/j.mad.2019.111175_bib0330","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.3892\/mmr.2014.2484","article-title":"MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer\u2019s disease","volume":"10","author":"Liu","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.mad.2019.111175_bib0335","first-page":"761","article-title":"The preliminary study on the diagnostic value of plasma exosomes microRNA-29c in the early diagnosis of the Alzheimer\u2019s disease","volume":"5","author":"Liu","year":"2018","journal-title":"Chin J Lab Diagn."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0340","first-page":"87","article-title":"The serum exosome derived MicroRNA-135a, -193b, and -384 were potential Alzheimer\u2019s disease biomarkers","volume":"31","author":"Yang","year":"2018","journal-title":"Biomed. Environ. Sci."},{"key":"10.1016\/j.mad.2019.111175_bib0345","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.neuroscience.2018.03.016","article-title":"Serum exosomal miR-223 serves as a potential diagnostic and prognostic biomarker for dementia","volume":"379","author":"Wei","year":"2018","journal-title":"Neuroscience."},{"issue":"35","key":"10.1016\/j.mad.2019.111175_bib0350","doi-asserted-by":"crossref","first-page":"37043","DOI":"10.18632\/oncotarget.6158","article-title":"Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease","volume":"6","author":"Gui","year":"2015","journal-title":"Oncotarget."},{"key":"10.1016\/j.mad.2019.111175_bib0355","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","author":"Sudhof","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"issue":"4925","key":"10.1016\/j.mad.2019.111175_bib0360","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1126\/science.2506642","article-title":"Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins","volume":"245","author":"S\u00fcdhof","year":"1989","journal-title":"Science"},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0365","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3233\/JAD-2005-7203","article-title":"Differential loss of synaptic proteins in Alzheimer\u2019s disease: implications for synaptic dysfunction","volume":"7","author":"Reddy","year":"2005","journal-title":"J. Alzheimers Dis."},{"issue":"9","key":"10.1016\/j.mad.2019.111175_bib0370","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/nn.2621","article-title":"Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons","volume":"13","author":"Chang","year":"2010","journal-title":"Nat. Neurosci."},{"issue":"7215","key":"10.1016\/j.mad.2019.111175_bib0375","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/nature07456","article-title":"Neuroligins and neurexins link synaptic function to cognitive disease","volume":"455","author":"S\u00fcdhof","year":"2008","journal-title":"Nature"},{"issue":"12","key":"10.1016\/j.mad.2019.111175_bib0380","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1096\/fj.201600816R","article-title":"Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer\u2019s disease","volume":"30","author":"Goetzl","year":"2016","journal-title":"FASEB J."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0385","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1096\/fj.14-262048","article-title":"Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer\u2019s disease","volume":"29","author":"Kapogiannis","year":"2015","journal-title":"FASEB J."},{"issue":"2","key":"10.1016\/j.mad.2019.111175_bib0390","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3233\/JAD-180578","article-title":"Extracellular vesicle biomarkers track cognitive changes following intranasal insulin in Alzheimer\u2019s disease","volume":"69","author":"Mustapic","year":"2019","journal-title":"J Alzheimers Dis."},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0395","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1212\/WNL.0000000000001702","article-title":"Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease","volume":"85","author":"Goetzl","year":"2015","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.mad.2019.111175_bib0400","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/ana.25172","article-title":"High complement levels in astrocyte-derived exosomes of Alzheimer disease","volume":"83","author":"Goetzl","year":"2018","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.mad.2019.111175_bib0405","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.dadm.2018.11.002","article-title":"Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer\u2019s disease dementia","volume":"11","author":"Winston","year":"2019","journal-title":"Alzheimers Dement (Amst)."},{"issue":"7493","key":"10.1016\/j.mad.2019.111175_bib0410","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nature13163","article-title":"REST and stress resistance in ageing and Alzheimer\u2019s disease","volume":"507","author":"Lu","year":"2014","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.mad.2019.111175_bib0415","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neuron.2014.08.048","article-title":"Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer\u2019s disease","volume":"84","author":"Liu","year":"2014","journal-title":"Neuron"},{"issue":"12","key":"10.1016\/j.mad.2019.111175_bib0420","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1093\/gerona\/glv165","article-title":"Cranberry extract standardized for proanthocyanidins alleviates \u03b2-amyloid peptide toxicity by improving proteostasis through HSF-1 in caenorhabditis elegans model of Alzheimer\u2019s disease","volume":"71","author":"Guo","year":"2016","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"issue":"7","key":"10.1016\/j.mad.2019.111175_bib0425","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/acn3.211","article-title":"Low neural exosomal levels of cellular survival factors in Alzheimer\u2019s disease","volume":"2","author":"Goetzl","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"issue":"4","key":"10.1016\/j.mad.2019.111175_bib0430","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbrc.2018.04.181","article-title":"Detection of the receptor for advanced glycation endproducts in neuronally-derived exosomes in plasma","volume":"500","author":"Patterson","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.mad.2019.111175_bib0435","doi-asserted-by":"crossref","DOI":"10.1007\/s13365-018-0695-4","article-title":"Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer\u2019s disease","author":"Pulliam","year":"2019","journal-title":"J. Neurovirol."},{"issue":"14","key":"10.1016\/j.mad.2019.111175_bib0440","doi-asserted-by":"crossref","first-page":"F9","DOI":"10.1097\/QAD.0000000000001595","article-title":"Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV","volume":"31","author":"Sun","year":"2017","journal-title":"AIDS"},{"issue":"6","key":"10.1016\/j.mad.2019.111175_bib0445","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/sj.ki.5002640","article-title":"The L1 cell adhesion molecule is a potential biomarker of human distal nephron injury in acute tubular necrosis","volume":"73","author":"Allory","year":"2008","journal-title":"Kidney Int."},{"key":"10.1016\/j.mad.2019.111175_bib0450","first-page":"3","article-title":"The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling","author":"Van Deun","year":"2014","journal-title":"J. Extracell. Vesicles."}],"container-title":["Mechanisms of Ageing and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0047637419301800?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0047637419301800?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:49:58Z","timestamp":1777466998000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0047637419301800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":90,"alternative-id":["S0047637419301800"],"URL":"https:\/\/doi.org\/10.1016\/j.mad.2019.111175","relation":{},"ISSN":["0047-6374"],"issn-type":[{"value":"0047-6374","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Extracellular vesicles as an emerging tool for the early detection of Alzheimer\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"Mechanisms of Ageing and Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mad.2019.111175","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"111175"}}