{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:48:25Z","timestamp":1790790505749,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,3,10]],"date-time":"2018-03-10T00:00:00Z","timestamp":1520640000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Astrocytes fulfill neuronal trophic roles normally, but are transformed in Alzheimer disease (AD) into A1\u2010type reactive astrocytes that may destroy neurons through unknown mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate astrocyte inflammatory mechanisms, astrocyte\u2010derived exosomes (ADEs) were isolated immunochemically from plasma samples of AD patients and matched controls for enzyme\u2010linked immunosorbent assay quantification of complement proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ADE levels of C1q, C4b, C3d, factor B, factor D, Bb, C3b, and C5b\u2010C9 terminal complement complex, but not mannose\u2010binding lectin, normalized by the CD81 exosome marker were significantly higher for AD patients (n\u2009=\u200928) than age\u2010 and gender\u2010matched controls (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). ADE normalized levels of interleukin (IL)\u20106, tumor necrosis factor\u2010\u03b1, and IL\u20101\u03b2 were significantly higher for AD patients than controls, but there was greater overlap between the two groups than for complement proteins. Mean ADE levels of complement proteins for AD patients in a longitudinal study were significantly higher (n\u2009=\u200916,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) at the AD2 stage of moderate dementia than at the AD1 preclinical stage 5 to 12 years earlier, which were the same as for controls. ADE levels of complement regulatory proteins CD59, CD46, decay\u2010accelerating factor (DAF), and complement receptor type 1, but not factor I, were significantly lower for AD patients than controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 for CD59 and DAF), were diminished by the AD1 stage, and were further decreased at the AD2 stage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>ADE complement effector proteins in AD are produced by dysregulated systems, attain higher levels than in controls, and may potentially damage neurons in the late inflammatory phase of AD. Ann Neurol 2018;83:544\u2013552<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25172","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T10:52:39Z","timestamp":1517914359000},"page":"544-552","source":"Crossref","is-referenced-by-count":351,"title":["High complement levels in astrocyte\u2010derived exosomes of Alzheimer disease"],"prefix":"10.1002","volume":"83","author":[{"given":"Edward J.","family":"Goetzl","sequence":"first","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco CA"},{"name":"Jewish Home of San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice B.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco CA"},{"name":"Jewish Home of San Francisco San Francisco CA"},{"name":"Department of Bioengineering University of California, San 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