{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T04:38:54Z","timestamp":1794544734754,"version":"4.9.1"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:00:00Z","timestamp":1503964800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:00:00Z","timestamp":1503964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["NIRG-14-316622"],"award-info":[{"award-number":["NIRG-14-316622"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["P30 NS050276"],"award-info":[{"award-number":["P30 NS050276"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["S10RR027990"],"award-info":[{"award-number":["S10RR027990"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG017617"],"award-info":[{"award-number":["AG017617"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG037693"],"award-info":[{"award-number":["AG037693"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG043375"],"award-info":[{"award-number":["AG043375"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG014449"],"award-info":[{"award-number":["AG014449"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1186\/s40478-017-0466-0","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T15:10:05Z","timestamp":1504019405000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities"],"prefix":"10.1186","volume":"5","author":[{"given":"S\u00e9bastien A.","family":"Gauthier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"P\u00e9rez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Ke","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Alldred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Pawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurjinder","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Ginsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Neubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-6763","authenticated-orcid":false,"given":"Efrat","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,29]]},"reference":[{"key":"466_CR1","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.3390\/ijms9112091","volume":"9","author":"MJ Alldred","year":"2008","unstructured":"Alldred MJ, Che S, Ginsberg SD (2008) Terminal Continuation (TC) RNA amplification enables expression profiling using minute RNA input obtained from mouse brain. Int J Mol Sci 9:2091\u20132104. doi: 10.3390\/ijms9112091","journal-title":"Int J Mol Sci"},{"key":"466_CR2","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.nbd.2011.10.022","volume":"45","author":"MJ Alldred","year":"2012","unstructured":"Alldred MJ, Duff KE, Ginsberg SD (2012) Microarray analysis of CA1 pyramidal neurons in a mouse model of tauopathy reveals progressive synaptic dysfunction. Neurobiol Dis 45:751\u2013762 doi:S0969\u20139961(11)00354\u20138","journal-title":"Neurobiol Dis"},{"key":"466_CR3","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1007\/s00429-014-0839-0","volume":"220","author":"MJ Alldred","year":"2015","unstructured":"Alldred MJ, Lee SH, Petkova E, Ginsberg SD (2015) Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer's disease (AD). Brain Struct Funct 220:2983\u20132996. doi: 10.1007\/s00429-014-0839-0","journal-title":"Brain Struct Funct"},{"key":"466_CR4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1002\/cne.23663","volume":"523","author":"MJ Alldred","year":"2015","unstructured":"Alldred MJ, Lee SH, Petkova E, Ginsberg SD (2015) Expression profile analysis of vulnerable CA1 pyramidal neurons in young-Middle-Aged Ts65Dn mice. J Comp Neurol 523:61\u201374. doi: 10.1002\/cne.23663","journal-title":"J Comp Neurol"},{"key":"466_CR5","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nbt.1807","volume":"29","author":"L Alvarez-Erviti","year":"2011","unstructured":"Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341\u2013345. doi: 10.1038\/nbt.1807","journal-title":"Nat Biotechnol"},{"key":"466_CR6","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nn.4132","volume":"18","author":"H Asai","year":"2015","unstructured":"Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, Wolozin B, Butovsky O, Kugler S, Ikezu T (2015) Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 18:1584\u20131593. doi: 10.1038\/nn.4132","journal-title":"Nat Neurosci"},{"key":"466_CR7","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.1523\/JNEUROSCI.17-16-06142.1997","volume":"17","author":"AM Cataldo","year":"1997","unstructured":"Cataldo AM, Barnett JL, Pieroni C, Nixon RA (1997) Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased beta-amyloidogenesis. J Neurosci 17:6142\u20136151","journal-title":"J Neurosci"},{"key":"466_CR8","doi-asserted-by":"publisher","first-page":"370","DOI":"10.2353\/ajpath.2008.071053","volume":"173","author":"AM Cataldo","year":"2008","unstructured":"Cataldo AM, Mathews PM, Boiteau AB, Hassinger LC, Peterhoff CM, Jiang Y, Mullaney K, Neve RL, Gruenberg J, Nixon RA (2008) Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects. Am J Pathol 173:370\u2013384 doi:S0002\u20139440(10)61614\u20138","journal-title":"Am J Pathol"},{"key":"466_CR9","doi-asserted-by":"crossref","first-page":"6788","DOI":"10.1523\/JNEUROSCI.23-17-06788.2003","volume":"23","author":"AM Cataldo","year":"2003","unstructured":"Cataldo AM, Petanceska S, Peterhoff CM, Terio NB, Epstein CJ, Villar A, Carlson EJ, Staufenbiel M, Nixon RA (2003) App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. J Neurosci 23:6788\u20136792 doi:23\/17\/6788","journal-title":"J Neurosci"},{"key":"466_CR10","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S0002-9440(10)64538-5","volume":"157","author":"AM Cataldo","year":"2000","unstructured":"Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157:277\u2013286 doi:S0002\u20139440(10)64538\u20135","journal-title":"Am J Pathol"},{"key":"466_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1042\/BJ20082422","volume":"420","author":"S Charrin","year":"2009","unstructured":"Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E (2009) Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 420:133\u2013154 doi:BJ20082422","journal-title":"Biochem J"},{"key":"466_CR12","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","volume":"30","author":"M Colombo","year":"2014","unstructured":"Colombo M, Raposo G, Thery C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255\u2013289. doi: 10.1146\/annurev-cellbio-101512-122326","journal-title":"Annu Rev Cell Dev Biol"},{"key":"466_CR13","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nprot.2009.36","volume":"4","author":"J Cox","year":"2009","unstructured":"Cox J, Matic I, Hilger M, Nagaraj N, Selbach M, Olsen JV, Mann M (2009) A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat Protoc 4:698\u2013705. doi: 10.1038\/nprot.2009.36","journal-title":"Nat Protoc"},{"key":"466_CR14","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","volume":"10","author":"J Cox","year":"2011","unstructured":"Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10:1794\u20131805. doi: 10.1021\/pr101065j","journal-title":"J Proteome Res"},{"key":"466_CR15","first-page":"263","volume":"360","author":"MT Davisson","year":"1990","unstructured":"Davisson MT, Schmidt C, Akeson EC (1990) Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog Clin Biol Res 360:263\u2013280","journal-title":"Prog Clin Biol Res"},{"key":"466_CR16","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1016\/j.neurobiolaging.2014.02.012","volume":"35","author":"MB Dinkins","year":"2014","unstructured":"Dinkins MB, Dasgupta S, Wang G, Zhu G, 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\u20131800 doi:S0197\u20134580(14)00204\u20138","journal-title":"Neurobiol Aging"},{"key":"466_CR17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.arr.2016.05.001","volume":"32","author":"E Eitan","year":"2016","unstructured":"Eitan E, Suire C, Zhang S, Mattson MP (2016) Impact of lysosome status on extracellular vesicle content and release. Ageing Res Rev 32:65\u201374 doi:S1568\u20131637(16)30077\u20130","journal-title":"Ageing Res Rev"},{"key":"466_CR18","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3233\/JAD-2010-101080","volume":"22","author":"SD Ginsberg","year":"2010","unstructured":"Ginsberg SD, Mufson EJ, Counts SE, Wuu J, Alldred MJ, Nixon RA, Che S (2010) Regional selectivity of rab5 and rab7 protein upregulation in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis 22:631\u2013639 doi:30718UGL13V2H023","journal-title":"J Alzheimers Dis"},{"key":"466_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13024-017-0165-0","volume":"12","author":"FX Guix","year":"2017","unstructured":"Guix FX, Sannerud R, Berditchevski F, Arranz AM, Horre K, Snellinx A, Thathiah A, Saido T, Saito T, Rajesh S, Overduin M, Kumar-Singh S, Radaelli E, Corthout N, Colombelli J, Tosi S, Munck S, Salas IH, Annaert W, De Strooper B (2017) Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments. Mol Neurodegener 12:25. doi: 10.1186\/s13024-017-0165-010.1186\/s13024-017-0165-0","journal-title":"Mol Neurodegener"},{"key":"466_CR20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2174\/1567205012666150921095505","volume":"13","author":"ED Hamlett","year":"2016","unstructured":"Hamlett ED, Boger HA, Ledreux A, Kelley CM, Mufson EJ, Falangola MF, Guilfoyle DN, Nixon RA, Patterson D, Duval N, Granholm AC (2016) Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome. Curr Alzheimer Res 13:35\u201352 doi:CAR-EPUB-70523","journal-title":"Curr Alzheimer Res"},{"key":"466_CR21","doi-asserted-by":"publisher","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, Clark D, Carroll SL, Carmona-Iragui M, Fortea J, Mufson EJ, Sabbagh M, Mohammed AH, Hartley D, Doran E, Lott IT, Granholm AC (2017) Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome. Alzheimers Dement 13:541\u2013549. doi: 10.1016\/j.jalz.2016.08.012","journal-title":"Alzheimers Dement"},{"key":"466_CR22","doi-asserted-by":"publisher","first-page":"13333","DOI":"10.1073\/pnas.93.23.13333","volume":"93","author":"DM Holtzman","year":"1996","unstructured":"Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC (1996) Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci U S A 93:13333\u201313338","journal-title":"Proc Natl Acad Sci U S A"},{"key":"466_CR23","doi-asserted-by":"publisher","first-page":"26589","DOI":"10.1074\/jbc.R116.757955","volume":"291","author":"J Howitt","year":"2016","unstructured":"Howitt J, Hill AF (2016) Exosomes in the Pathology of Neurodegenerative Diseases. J Biol Chem 291:26589\u201326597. doi: 10.1074\/jbc.R116.757955","journal-title":"J Biol Chem"},{"key":"466_CR24","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1083\/jcb.200911018","volume":"189","author":"C Hsu","year":"2010","unstructured":"Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Gronborg M, Mobius W, Rhee J, Barr FA, Simons M (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223\u2013232. doi: 10.1083\/jcb.200911018","journal-title":"J Cell Biol"},{"key":"466_CR25","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1093\/brain\/aww237","volume":"139","author":"Y Iguchi","year":"2016","unstructured":"Iguchi Y, Eid L, Parent M, Soucy G, Bareil C, Riku Y, Kawai K, Takagi S, Yoshida M, Katsuno M, Sobue G, Julien JP (2016) Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain 139:3187\u20133201 doi:aww237","journal-title":"Brain"},{"key":"466_CR26","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.neurobiolaging.2015.11.013","volume":"39","author":"Y Jiang","year":"2016","unstructured":"Jiang Y, Rigoglioso A, Peterhoff CM, Pawlik M, Sato Y, Bleiwas C, Stavrides P, Smiley JF, Ginsberg SD, Mathews PM, Levy E, Nixon RA (2016) Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF. Neurobiol Aging 39:90\u201398 doi:S0197\u20134580(15)00580\u20131","journal-title":"Neurobiol Aging"},{"key":"466_CR27","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1182\/blood.V74.5.1844.1844","volume":"74","author":"RM Johnstone","year":"1989","unstructured":"Johnstone RM, Bianchini A, Teng K (1989) Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. Blood 74:1844\u20131851","journal-title":"Blood"},{"key":"466_CR28","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3390\/ijms17020170","volume":"17","author":"H Kalra","year":"2016","unstructured":"Kalra H, Drummen GP, Mathivanan S (2016) Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int J Mol Sci 17:170. doi: 10.3390\/ijms17020170","journal-title":"Int J Mol Sci"},{"key":"466_CR29","doi-asserted-by":"publisher","first-page":"5099","DOI":"10.1523\/JNEUROSCI.5338-13.2014","volume":"34","author":"G Kaur","year":"2014","unstructured":"Kaur G, Sharma A, Xu W, Gerum S, Alldred MJ, Subbanna S, Basavarajappa BS, Pawlik M, Ohno M, Ginsberg SD, Wilson DA, Guilfoyle DN, Levy E (2014) Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome. J Neurosci 34:5099\u20135106 doi:34\/15\/5099","journal-title":"J Neurosci"},{"key":"466_CR30","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ceb.2014.05.004","volume":"29","author":"J Kowal","year":"2014","unstructured":"Kowal J, Tkach M, Thery C (2014) Biogenesis and secretion of exosomes. Curr Opin Cell Biol 29:116\u2013125 doi:S0955\u20130674(14)00057-X","journal-title":"Curr Opin Cell Biol"},{"key":"466_CR31","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/npp.2015.242","volume":"41","author":"EM Kramer-Albers","year":"2016","unstructured":"Kramer-Albers EM, Ping Kuo-Elsner W (2016) Extracellular Vesicles: Goodies for the Brain? Neuropsychopharmacology 41:371\u2013372. doi: 10.1038\/npp.2015.242","journal-title":"Neuropsychopharmacology"},{"key":"466_CR32","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.yexmp.2008.10.006","volume":"86","author":"S Levine","year":"2009","unstructured":"Levine S, Saltzman A, Levy E, Ginsberg SD (2009) Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease. Exp Mol Pathol 86:18\u201322 doi:S0014\u20134800(08)00113\u20135","journal-title":"Exp Mol Pathol"},{"key":"466_CR33","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s10571-015-0314-3","volume":"36","author":"R Lopez-Leal","year":"2016","unstructured":"Lopez-Leal R, Court FA (2016) Schwann Cell Exosomes Mediate Neuron-Glia Communication and Enhance Axonal Regeneration. Cell Mol Neurobiol 36:429\u2013436. doi: 10.1007\/s10571-015-0314-310.1007\/s10571-015-0314-3","journal-title":"Cell Mol Neurobiol"},{"key":"466_CR34","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/glia.22558","volume":"61","author":"MA Lopez-Verrilli","year":"2013","unstructured":"Lopez-Verrilli MA, Picou F, Court FA (2013) Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 61:1795\u20131806. doi: 10.1002\/glia.22558","journal-title":"Glia"},{"key":"466_CR35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/B978-0-444-54299-1.00006-6","volume":"197","author":"IT Lott","year":"2012","unstructured":"Lott IT (2012) Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 197:101\u2013121 doi:B978\u20130\u2013444-54299-1.00006-6","journal-title":"Prog Brain Res"},{"key":"466_CR36","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/S1474-4422(10)70112-5","volume":"9","author":"IT Lott","year":"2010","unstructured":"Lott IT, Dierssen M (2010) Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Lancet Neurol 9:623\u2013633 doi:S1474\u20134422(10)70112\u20135","journal-title":"Lancet Neurol"},{"key":"466_CR37","volume-title":"Generalized, Linear, and Mixed Models","author":"CE McCulloch","year":"2011","unstructured":"McCulloch CE, Searle SR, Neuhaus JM (2011) Generalized, Linear, and Mixed Models, Second edn. John Wiley & Sons, New York","edition":"Second"},{"key":"466_CR38","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jdermsci.2016.06.013","volume":"84","author":"K Nakamura","year":"2016","unstructured":"Nakamura K, Jinnin M, Harada M, Kudo H, Nakayama W, Inoue K, Ogata A, Kajihara I, Fukushima S, Ihn H (2016) Altered expression of CD63 and exosomes in scleroderma dermal fibroblasts. J Dermatol Sci 84:30\u201339 doi:S0923\u20131811(16)30130-X","journal-title":"J Dermatol Sci"},{"key":"466_CR39","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S0002-9440(10)63163-X","volume":"164","author":"RA Nixon","year":"2004","unstructured":"Nixon RA (2004) Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up. Am J Pathol 164:757\u2013761 doi:S0002\u20139440(10)63163-X","journal-title":"Am J Pathol"},{"key":"466_CR40","doi-asserted-by":"publisher","first-page":"43108","DOI":"10.1074\/jbc.M112.404467","volume":"287","author":"R Perez-Gonzalez","year":"2012","unstructured":"Perez-Gonzalez R, Gauthier SA, Kumar A, Levy E (2012) The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J Biol Chem 287:43108\u201343115 doi:M112.404467","journal-title":"J Biol Chem"},{"key":"466_CR41","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-1-4939-6728-5_10","volume":"1545","author":"R Perez-Gonzalez","year":"2017","unstructured":"Perez-Gonzalez R, Gauthier SA, Kumar A, Saito M, Levy E (2017) A Method for Isolation of Extracellular Vesicles and Characterization of Exosomes from Brain Extracellular Space. Methods Mol Biol 1545:139\u2013151. doi: 10.1007\/978-1-4939-6728-5_10","journal-title":"Methods Mol Biol"},{"key":"466_CR42","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.yexcr.2008.09.020","volume":"315","author":"MS Pols","year":"2009","unstructured":"Pols MS, Klumperman J (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res 315:1584\u20131592 doi:S0014\u20134827(08)00393\u20135","journal-title":"Exp Cell Res"},{"key":"466_CR43","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/nprot.2007.261","volume":"2","author":"J Rappsilber","year":"2007","unstructured":"Rappsilber J, Mann M, Ishihama Y (2007) Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc 2:1896\u20131906 doi:nprot.2007.261","journal-title":"Nat Protoc"},{"key":"466_CR44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuron.2006.05.022","volume":"51","author":"A Salehi","year":"2006","unstructured":"Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC (2006) Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51:29\u201342 doi:S0896\u20136273(06)00414\u20134","journal-title":"Neuron"},{"key":"466_CR45","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3389\/fnins.2017.00082","volume":"11","author":"DK Sarko","year":"2017","unstructured":"Sarko DK, McKinney CE (2017) Exosomes: Origins and Therapeutic Potential for Neurodegenerative Disease. Front Neurosci 11:82. doi: 10.3389\/fnins.2017.00082","journal-title":"Front Neurosci"},{"key":"466_CR46","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1242\/jcs.115.12.2505","volume":"115","author":"A Savina","year":"2002","unstructured":"Savina A, Vidal M, Colombo MI (2002) The exosome pathway in K562 cells is regulated by Rab11. J Cell Sci 115:2505\u20132515","journal-title":"J Cell Sci"},{"key":"466_CR47","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.1074\/mcp.M114.043489","volume":"13","author":"RA Scheltema","year":"2014","unstructured":"Scheltema RA, Hauschild JP, Lange O, Hornburg D, Denisov E, Damoc E, Kuehn A, Makarov A, Mann M (2014) The Q Exactive HF, a Benchtop mass spectrometer with a pre-filter, high-performance quadrupole and an ultra-high-field Orbitrap analyzer. Mol Cell Proteomics 13:3698\u20133708. doi: 10.1074\/mcp.M114.043489","journal-title":"Mol Cell Proteomics"},{"key":"466_CR48","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1021\/ac950914h","volume":"68","author":"A Shevchenko","year":"1996","unstructured":"Shevchenko A, Wilm M, Vorm O, Mann M (1996) Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem 68:850\u2013858","journal-title":"Anal Chem"},{"key":"466_CR49","doi-asserted-by":"publisher","first-page":"26279","DOI":"10.1074\/jbc.M110.134775","volume":"285","author":"K Strauss","year":"2010","unstructured":"Strauss K, Goebel C, Runz H, Mobius W, Weiss S, Feussner I, Simons M, Schneider A (2010) Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann-Pick type C disease. J Biol Chem 285:26279\u201326288. doi: 10.1074\/jbc.M110.134775","journal-title":"J Biol Chem"},{"key":"466_CR50","doi-asserted-by":"publisher","first-page":"Unit 3 22","DOI":"10.1002\/0471143030.cb0322s30","volume":"Chapter 3","author":"C Thery","year":"2006","unstructured":"Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3:Unit 3 22. doi: 10.1002\/0471143030.cb0322s30","journal-title":"Curr Protoc Cell Biol"},{"key":"466_CR51","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1124\/pr.112.005983","volume":"64","author":"E van der Pol","year":"2012","unstructured":"van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64:676\u2013705. doi: 10.1124\/pr.112.005983","journal-title":"Pharmacol Rev"},{"key":"466_CR52","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00335-004-2428-7","volume":"16","author":"AJ Villar","year":"2005","unstructured":"Villar AJ, Belichenko PV, Gillespie AM, Kozy HM, Mobley WC, Epstein CJ (2005) Identification and characterization of a new Down syndrome model, Ts[Rb(12.1716)]2Cje, resulting from a spontaneous Robertsonian fusion between T(171)65Dn and mouse chromosome 12. Mamm Genome 16:79\u201390","journal-title":"Mamm Genome"},{"key":"466_CR53","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1750-1326-9-31","volume":"9","author":"X Wang","year":"2014","unstructured":"Wang X, Huang T, Bu G, Xu H (2014) Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegener 9:31. doi: 10.1186\/1750-1326-9-31","journal-title":"Mol Neurodegener"},{"key":"466_CR54","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1056\/NEJM198411013111818","volume":"311","author":"KE Wisniewski","year":"1984","unstructured":"Wisniewski KE, Laure-Kamionowska M, Wisniewski HM (1984) Evidence of arrest of neurogenesis and synaptogenesis in brains of patients with Down's syndrome. N Engl J Med 311:1187\u20131188. doi: 10.1056\/NEJM198411013111818","journal-title":"N Engl J Med"},{"key":"466_CR55","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/ana.410170310","volume":"17","author":"KE Wisniewski","year":"1985","unstructured":"Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol 17:278\u2013282. doi: 10.1002\/ana.410170310","journal-title":"Ann Neurol"},{"key":"466_CR56","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40035-017-0072-x","volume":"6","author":"T Xiao","year":"2017","unstructured":"Xiao T, Zhang W, Jiao B, Pan CZ, Liu X, Shen L (2017) The role of exosomes in the pathogenesis of Alzheimer' disease. Transl Neurodegener 6:3. doi: 10.1186\/s40035-017-0072-x72","journal-title":"Transl Neurodegener"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-017-0466-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40478-017-0466-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-017-0466-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T22:24:32Z","timestamp":1659392672000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-017-0466-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,29]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["466"],"URL":"https:\/\/doi.org\/10.1186\/s40478-017-0466-0","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,29]]},"assertion":[{"value":"17 August 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal procedures were performed following the National Institutes of Health guidelines with approval from the Institutional Animal Care and Use Committee at the Nathan S. Kline Institute for Psychiatric Research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"65"}}