{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:21:03Z","timestamp":1791271263123,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T00:00:00Z","timestamp":1367452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50AG05134"],"award-info":[{"award-number":["P50AG05134"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:p>\n                    There is a growing body of evidence that soluble oligomeric forms of amyloid \u03b2 (A\u03b2) play a critical role in Alzheimer's disease (AD). Despite the importance of soluble A\u03b2 oligomers as a therapeutic target for AD, the dynamic metabolism of these A\u03b2 species\n                    <jats:italic>in vivo<\/jats:italic>\n                    has not been elucidated because of the difficulty in monitoring brain A\u03b2 oligomers in living animals. Here, using a unique large pore\u2010sized membrane microdialysis, we characterized soluble A\u03b2 oligomers in brain interstitial fluid (ISF) of awake, freely moving APP\/PS1 transgenic and control WT mice. We could detect high\u2010molecular\u2010weight (HMW) and low\u2010molecular\u2010weight (LMW) A\u03b2 oligomers in the brain ISF of living animals, which increased dramatically in an age\u2010dependent manner (5\u2010 to 8\u2010fold increase, 4\n                    <jats:italic>vs.<\/jats:italic>\n                    17\u201018 mo). Notably, HMW A\u03b2 decreased more slowly than other forms of A\u03b2 after acute \u03b3\u2010secretase inhibition [% decrease from the baseline (HMW\n                    <jats:italic>vs.<\/jats:italic>\n                    LMW) was 36.9\n                    <jats:italic>vs.<\/jats:italic>\n                    74.1% (A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) and 25.4\n                    <jats:italic>vs.<\/jats:italic>\n                    88.0% (A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01)], suggesting that HMW A\u03b2 oligomers clear more slowly than other forms from the brain. These data reveal the dynamic metabolism of neurotoxic A\u03b2 oligomers in AD brain and could provide new insights into A\u03b2\u2010targeted therapies for AD.\u2014Takeda, S., Hashimoto, T., Roe, A. D., Hori, Y., Spires\u2010Jones, T. L.and Hyman, B. T., Brain interstitial oligomeric amyloid \u03b2 increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. FASEB J. 27, 3239\u20133248 (2013).\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.13-229666","type":"journal-article","created":{"date-parts":[[2013,5,3]],"date-time":"2013-05-03T00:43:54Z","timestamp":1367541834000},"page":"3239-3248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Brain interstitial oligomeric amyloid \u03b2 increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease"],"prefix":"10.1096","volume":"27","author":[{"given":"Shuko","family":"Takeda","sequence":"first","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson D.","family":"Roe","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hori","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara L.","family":"Spires\u2010Jones","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Laboratory Department of Neurology MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002369"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8508"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00205-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/990114"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5440.735"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2005.11.003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04426.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04533"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/416535a"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1782"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4970-06.2007"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.05.012"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811698106"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-26-08844.2003"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3272-11.2011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2801"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1180962"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2620"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00850-X"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1542-12.2012"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.022"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050004797"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.04.035"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-150359"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1071"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.103754"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2008.565"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.017"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws127"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2021-09.2009"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-229666","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.13-229666","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-229666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:39:30Z","timestamp":1761669570000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.13-229666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,2]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1096\/fj.13-229666"],"URL":"https:\/\/doi.org\/10.1096\/fj.13-229666","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,2]]},"assertion":[{"value":"2013-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}