{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:32:39Z","timestamp":1792402359887,"version":"4.4.0"},"reference-count":54,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T00:00:00Z","timestamp":1416528000000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,5,21]]},"abstract":"<jats:p>Apolipoprotein E (apoE) is the strongest known genetic risk factor for late onset Alzheimer's disease (AD). It influences amyloid-\u03b2 (A\u03b2) clearance and aggregation, which likely contributes in large part to its role in AD pathogenesis. We recently found that HJ6.3, a monoclonal antibody against apoE, significantly reduced A\u03b2 plaque load when given to APPswe\/PS1\u0394E9 (APP\/PS1) mice starting before the onset of plaque deposition. To determine whether the anti-apoE antibody HJ6.3 affects A\u03b2 plaques, neuronal network function, and behavior in APP\/PS1 mice after plaque onset, we administered HJ6.3 (10 mg\/kg\/week) or PBS intraperitoneally to 7-month-old APP\/PS1 mice for 21 weeks. HJ6.3 mildly improved spatial learning performance in the water maze, restored resting-state functional connectivity, and modestly reduced brain A\u03b2 plaque load. There was no effect of HJ6.3 on total plasma cholesterol or cerebral amyloid angiopathy. To investigate the underlying mechanisms of anti-apoE immunotherapy, HJ6.3 was applied to the brain cortical surface and amyloid deposition was followed over 2 weeks using<jats:italic>in vivo<\/jats:italic>imaging. Acute exposure to HJ6.3 affected the course of amyloid deposition in that it prevented the formation of new amyloid deposits, limited their growth, and was associated with occasional clearance of plaques, a process likely associated with direct binding to amyloid aggregates. Topical application of HJ6.3 for only 14 d also decreased the density of amyloid plaques assessed postmortem. Collectively, these studies suggest that anti-apoE antibodies have therapeutic potential when given before or after the onset of A\u03b2 pathology.<\/jats:p>","DOI":"10.1523\/jneurosci.0646-14.2014","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T17:05:00Z","timestamp":1400691900000},"page":"7281-7292","source":"Crossref","is-referenced-by-count":125,"title":["Anti-ApoE Antibody Given after Plaque Onset Decreases A\u03b2 Accumulation and Improves Brain Function in a Mouse Model of A\u03b2 Amyloidosis"],"prefix":"10.1523","volume":"34","author":[{"given":"Fan","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise","family":"Hudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam Q.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Mahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katheryn B.","family":"Lefton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony J.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T.","family":"Dearborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungsu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Culver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Betensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2014,5,21]]},"reference":[{"key":"2023041304110011000_34.21.7281.1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3233\/JAD-2002-4303","article-title":"ApoE4: is it the absence of good or the presence of bad?","volume":"4","author":"Ashford","year":"2002","journal-title":"J Alzheimers Dis"},{"key":"2023041304110011000_34.21.7281.2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200209000-00001"},{"key":"2023041304110011000_34.21.7281.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15233"},{"key":"2023041304110011000_34.21.7281.4","doi-asserted-by":"publisher","DOI":"10.1038\/78682"},{"key":"2023041304110011000_34.21.7281.5","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1065"},{"key":"2023041304110011000_34.21.7281.6","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2801"},{"key":"2023041304110011000_34.21.7281.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5845-11.2012"},{"key":"2023041304110011000_34.21.7281.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0033-12.2012"},{"key":"2023041304110011000_34.21.7281.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125529"},{"key":"2023041304110011000_34.21.7281.10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"2023041304110011000_34.21.7281.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206446109"},{"key":"2023041304110011000_34.21.7281.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"2023041304110011000_34.21.7281.13","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"2023041304110011000_34.21.7281.14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36663"},{"key":"2023041304110011000_34.21.7281.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067568"},{"key":"2023041304110011000_34.21.7281.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.029"},{"key":"2023041304110011000_34.21.7281.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409072102"},{"key":"2023041304110011000_34.21.7281.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1051-10.2010"},{"key":"2023041304110011000_34.21.7281.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504136102"},{"key":"2023041304110011000_34.21.7281.20","unstructured":"Franklin KB Paxinos G (1996) The mouse brain in stereotaxic coordinates (Academic, San Diego), Ed 1."},{"key":"2023041304110011000_34.21.7281.21","doi-asserted-by":"crossref","first-page":"7889","DOI":"10.1523\/JNEUROSCI.23-21-07889.2003","article-title":"Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice","volume":"23","author":"Fryer","year":"2003","journal-title":"J Neurosci"},{"key":"2023041304110011000_34.21.7281.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"2023041304110011000_34.21.7281.23","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200006)47:6<739::AID-ANA6>3.0.CO;2-8"},{"key":"2023041304110011000_34.21.7281.24","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002369"},{"key":"2023041304110011000_34.21.7281.25","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007000"},{"key":"2023041304110011000_34.21.7281.26","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh019"},{"key":"2023041304110011000_34.21.7281.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.04.010"},{"key":"2023041304110011000_34.21.7281.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.013"},{"key":"2023041304110011000_34.21.7281.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3773-11.2011"},{"key":"2023041304110011000_34.21.7281.30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121274"},{"key":"2023041304110011000_34.21.7281.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411420200"},{"key":"2023041304110011000_34.21.7281.32","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.219"},{"key":"2023041304110011000_34.21.7281.33","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.t01-1-00216.x"},{"key":"2023041304110011000_34.21.7281.34","doi-asserted-by":"publisher","DOI":"10.1038\/372092a0"},{"key":"2023041304110011000_34.21.7281.35","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91092-F"},{"key":"2023041304110011000_34.21.7281.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078259"},{"key":"2023041304110011000_34.21.7281.37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4337-04.2005"},{"key":"2023041304110011000_34.21.7281.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604011103"},{"key":"2023041304110011000_34.21.7281.39","doi-asserted-by":"publisher","DOI":"10.1038\/22124"},{"key":"2023041304110011000_34.21.7281.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1879-05.2005"},{"key":"2023041304110011000_34.21.7281.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"2023041304110011000_34.21.7281.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.8098"},{"key":"2023041304110011000_34.21.7281.43","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3233\/JAD-2002-4305","article-title":"The presence of apoE4, not the absence of apoE3, contributes to AD pathology","volume":"4","author":"Teter","year":"2002","journal-title":"J Alzheimers Dis"},{"key":"2023041304110011000_34.21.7281.44","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-1053-1"},{"key":"2023041304110011000_34.21.7281.45","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00744-4"},{"key":"2023041304110011000_34.21.7281.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.03.058"},{"key":"2023041304110011000_34.21.7281.47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016322"},{"key":"2023041304110011000_34.21.7281.48","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1523\/JNEUROSCI.23-09-03745.2003","article-title":"Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation","volume":"23","author":"Wilcock","year":"2003","journal-title":"J Neurosci"},{"key":"2023041304110011000_34.21.7281.49","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-1-24"},{"key":"2023041304110011000_34.21.7281.50","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1090-04.2004"},{"key":"2023041304110011000_34.21.7281.51","first-page":"1030","article-title":"Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro","volume":"145","author":"Wisniewski","year":"1994","journal-title":"Am J Pathol"},{"key":"2023041304110011000_34.21.7281.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.08.006"},{"key":"2023041304110011000_34.21.7281.53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2021-09.2009"},{"key":"2023041304110011000_34.21.7281.54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701096104"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0646-14.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T22:07:33Z","timestamp":1681423653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0646-14.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,21]]},"references-count":54,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2014,5,21]]},"published-print":{"date-parts":[[2014,5,21]]}},"alternative-id":["10.1523\/JNEUROSCI.0646-14.2014"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0646-14.2014","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,21]]}}}