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Studies have shown that the binding between apoE and amyloid\u2010\u03b2 (A\u03b2) peptides occurs at residues 244\u2013272 of apoE and residues 12\u201328 of A\u03b2. ApoE4 has been implicated in promoting A\u03b2 deposition and impairing clearance of A\u03b2. We hypothesized that blocking the apoE\/A\u03b2 interaction would serve as an effective new approach to AD therapy. We have previously shown that treatment with A\u03b212\u201028P can reduce amyloid plaques in APP\/PS1 transgenic (Tg) mice and vascular amyloid in TgSwDI mice with congophilic amyloid angiopathy. In the present study, we investigated whether the A\u03b212\u201028P elicits a therapeutic effect on tau\u2010related pathology in addition to amyloid pathology using old triple transgenic AD mice (3xTg, with PS1<jats:sub>M146V<\/jats:sub>, APP<jats:sub>Swe<\/jats:sub> and tau<jats:sub>P30IL<\/jats:sub> transgenes) with established pathology from the ages of 21 to 26\u00a0months. We show that treatment with A\u03b212\u201028P substantially reduces tau pathology both immunohistochemically and biochemically, as well as reducing the amyloid burden and suppressing the activation of astrocytes and microglia. These affects correlate with a behavioral amelioration in the treated Tg mice.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12484-fig-0013-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>The apolipoprotein E (apoE)\/amyloid beta (A\u03b2) interaction plays an important role in the aggregation and clearance of A\u03b2. We show that the apoE\/A\u03b2 binding blocker, A\u03b212\u201028P, elicits a therapeutic effect on tau related pathology, in addition to amyloid deposition, in 3xTg Alzheimer's disease model mice. These affects correlate with a behavioral amelioration in the treated Tg mice. We believe this presents a novel therapeutic approach for AD.<\/jats:p>","DOI":"10.1111\/jnc.12484","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T02:32:18Z","timestamp":1381545138000},"page":"577-591","source":"Crossref","is-referenced-by-count":56,"title":["Blocking the apolipoprotein E\/Amyloid \u03b2 interaction in triple transgenic mice ameliorates Alzheimer's disease related amyloid \u03b2 and tau pathology"],"prefix":"10.1111","volume":"128","author":[{"given":"Shan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology New York University School of Medicine ERSP New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Breitbart","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University School of Medicine ERSP New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University School of Medicine ERSP New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj D.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Immunology New York State Institute for Basic Research in Developmental Disabilities Staten Island NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allal","family":"Boutajangout","sequence":"additional","affiliation":[{"name":"Departments of Neurology Neuroscience and Psychiatry New York University School of Medicine ERSP New York NY USA"},{"name":"The King Abdulaziz University School of Medicine Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrieta","family":"Scholtzova","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University School of Medicine ERSP New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"Departments of Neurology Pathology and Psychiatry New York University School of Medicine ERSP New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05149.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2361-07.2007"},{"key":"e_1_2_7_4_1","unstructured":"BatschN. 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