{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:17:51Z","timestamp":1791425871354,"version":"4.3.3"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"36","license":[{"start":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T00:00:00Z","timestamp":1487894400000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["K99EY024690"],"award-info":[{"award-number":["K99EY024690"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["5 R21NS072556"],"award-info":[{"award-number":["5 R21NS072556"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS090934"],"award-info":[{"award-number":["R01 NS090934"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG047644"],"award-info":[{"award-number":["R01 AG047644"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2016M3C7A1905391"],"award-info":[{"award-number":["NRF-2016M3C7A1905391"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2016R1C1B3006969"],"award-info":[{"award-number":["NRF-2016R1C1B3006969"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,9,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Susceptibility to Alzheimer\u2019s disease (AD) is strongly controlled by apolipoprotein E (\n                    <jats:italic>APOE<\/jats:italic>\n                    ) genotype. The\n                    <jats:italic>E4<\/jats:italic>\n                    allele greatly increases risk whereas the\n                    <jats:italic>E2<\/jats:italic>\n                    allele decreases risk, but it is not known how the\n                    <jats:italic>APOE<\/jats:italic>\n                    allele controls AD risk. In this paper, we report a novel role for APOE by showing that APOE2 enhances and APOE4 decreases the rate of synapse pruning and turnover in the brain by astrocytes. We also show that\n                    <jats:italic>APOE<\/jats:italic>\n                    alleles control the rate of accumulation of the complement C1q protein, which we hypothesize, reflects senescent synapse accumulation during normal brain aging and vulnerability of the aging brain to neurodegenerative diseases such as AD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1609896113","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T23:08:49Z","timestamp":1472080129000},"page":"10186-10191","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":228,"title":["Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes"],"prefix":"10.1073","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-9007","authenticated-orcid":false,"given":"Won-Suk","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip B.","family":"Verghese","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrani","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Joung","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[{"name":"Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Charlestown, MA 02129;"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben A.","family":"Barres","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.225"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283935"},{"key":"e_1_3_3_4_2","first-page":"199","article-title":"Apolipoprotein E isotype-specific effects in neurodegeneration","volume":"3","author":"Teter B","year":"2000","unstructured":"B Teter, Apolipoprotein E isotype-specific effects in neurodegeneration. Alzheimers Rep 3, 199\u2013212 (2000).","journal-title":"Alzheimers Rep"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.022"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050004797"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1058"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409072102"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7715"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10914"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35006165"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.05.008"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4026-09.2009"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12776"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6366"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.07.022"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17630"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","unstructured":"M Aziz WL Yang P Wang Measurement of phagocytic engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester. Curr Protocols Immunol Chapter 14:Unit 14.31. (2013).","DOI":"10.1002\/0471142735.im1431s100"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.06.008"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-13"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220484110"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500114-JLR200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a003282"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31529-6"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.16.9039"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4178-07.2008"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03385"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3253"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.036"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.026"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44646"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1333-13.2013"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-34134-X_11"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.001"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2014.0248"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.040717"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2177"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6818"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.015"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.171"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.2144\/000112001"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.3.890"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34756-2"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi036305i"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1609896113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1609896113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:23:30Z","timestamp":1649813010000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1609896113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,24]]},"references-count":48,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2016,9,6]]}},"alternative-id":["10.1073\/pnas.1609896113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1609896113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,24]]},"assertion":[{"value":"2016-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}