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Plasma neuronal\u2010derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross\u2010sectional study, and from 9 patients with AD, 10with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts. NDE levels of synaptophysin, synaptopodin, synaptotagmin\u20102, and neurogranin were significantly lower in patients with FTD and ADthan in controls, but those of growth\u2010associated protein 43 and synapsin 1 were reduced only in patients with AD. Functionally relevant phosphorylation of synapsin 1 serine 9 was reduced in patients with FTD and AD, although total synapsin 1 protein was higher in FTD than in controls. NDE levels of synaptotagmin, synaptophysin, and neurograninwere decreased yearsbeforedementia inpatientswithFTD and AD.NDElevelsof synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid \u03b2\u2010peptide 42 or P\u2010T181\u2010tau, were correlated significantly with cognition assessed bymini\u2010mental state examination or AD assessment scale\u2010cognitive subscale. NDE synaptic proteins may be useful preclinical indices and progression measures in senile dementias.\u2014Goetzl, E. J., Kapogiannis, D., Schwartz, J. B., Lobach, I. V., Goetzl, L., Abner, E. L., Jicha, G. A., Karydas, A.M., Boxer, A., Miller, B. L. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease. FASEB J. 30, 4141\u20134148 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600816r","type":"journal-article","created":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T23:02:38Z","timestamp":1473202958000},"page":"4141-4148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":375,"title":["Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease"],"prefix":"10.1096","volume":"30","author":[{"given":"Edward J.","family":"Goetzl","sequence":"first","affiliation":[{"name":"Department of Medicine University of California, San Francisco  San Francisco California USA"},{"name":"Jewish Home of San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Kapogiannis","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice B.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California, San Francisco  San Francisco California USA"},{"name":"Department of Bioengineering University of California, San Francisco  San Francisco California USA"},{"name":"Jewish Home of San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna V.","family":"Lobach","sequence":"additional","affiliation":[{"name":"Clinical Translational Science Institute University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Goetzl","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology, and Reproductive Sciences Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin L.","family":"Abner","sequence":"additional","affiliation":[{"name":"Sanders\u2013Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Jicha","sequence":"additional","affiliation":[{"name":"Sanders\u2013Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Karydas","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Boxer","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2008.07.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.115"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22392"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270502"},{"key":"e_1_2_8_7_1","first-page":"235","article-title":"Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease","volume":"138","author":"Masliah E.","year":"1991","journal-title":"Am. 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