{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:10:04Z","timestamp":1789873804150,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"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":["AG056732"],"award-info":[{"award-number":["AG056732"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Down syndrome (DS) is a human genetic disease caused by trisomy of chromosome 21 and characterized by early developmental brain abnormalities. Dysfunctional endosomal pathway in neurons is an early event of DS and Alzheimer's disease. Recently, we have demonstrated that exosome secretion is upregulated in human DS postmortem brains, in the brain of the trisomic mouse model Ts[Rb(12.17<jats:sup>16<\/jats:sup>)]2Cje (Ts2) and by DS fibroblasts as compared with disomic controls. High levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Partially blocking exosome secretion by DS fibroblasts exacerbated a pre\u2010existing early endosomal pathology. We thus hypothesized that enhanced CD63 expression induces generation of intraluminal vesicles (ILVs) in late endosomes\/multivesicular bodies (MVBs), increasing exosome release as an endogenous mechanism to mitigate endosomal abnormalities in DS. Herein, we show a high\u2010resolution electron microscopy analysis of MVBs in neurons of the frontal cortex of 12\u2010month\u2010old Ts2 mice and littermate diploid controls. Our quantitative analysis revealed that Ts2 MVBs are larger, more abundant, and contain a higher number of ILVs per neuron compared to controls. These findings were further corroborated biochemically by Western blot analysis of purified endosomal fractions showing higher levels of ILVs proteins in the same fractions containing endosomal markers in the brain of Ts2 mice compared to controls. These data suggest that upregulation of ILVs production may be a key homeostatic mechanism to alleviate endosomal dysregulation via the endosomal\u2013exosomal pathway.<\/jats:p>","DOI":"10.1002\/dneu.22708","type":"journal-article","created":{"date-parts":[[2019,7,6]],"date-time":"2019-07-06T14:39:27Z","timestamp":1562423967000},"page":"656-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Enhanced generation of intraluminal vesicles in neuronal late endosomes in the brain of a Down syndrome mouse model with endosomal dysfunction"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7237-0076","authenticated-orcid":false,"given":"Pasquale","family":"D'Acunzo","sequence":"first","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"},{"name":"Department of Psychiatry New York University Langone Health  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Hargash","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris N.","family":"Goulbourne","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"P\u00e9rez\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"},{"name":"Department of Psychiatry New York University Langone Health  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efrat","family":"Levy","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan S. Kline Institute Orangeburg New York"},{"name":"Department of Psychiatry New York University Langone Health  New York New York"},{"name":"Department of Biochemistry &amp; Molecular Pharmacology New York University Langone Health  New York New York"},{"name":"Neuroscience Institute New York University Langone Health  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2502"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.10.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508632200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-16-06142.1997"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071053"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-17-06788.2003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64538-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.10.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.128868"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12139"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0466-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200911018"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.11.013"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.08.025"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5338-13.2014"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.97"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2008.10.006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00820.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20735"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy289"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.404467"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6728-5_10"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.09.020"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.20.8981-8993.2004"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153124"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-004-2428-7"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.01.003"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170310"}],"container-title":["Developmental Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdneu.22708","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dneu.22708","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dneu.22708","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dneu.22708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T02:01:37Z","timestamp":1694224897000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dneu.22708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/dneu.22708"],"URL":"https:\/\/doi.org\/10.1002\/dneu.22708","archive":["Portico"],"relation":{},"ISSN":["1932-8451","1932-846X"],"issn-type":[{"value":"1932-8451","type":"print"},{"value":"1932-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7]]},"assertion":[{"value":"2019-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}