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Studies have shown that apoE, apoE4 in particular, binds to amyloid-<jats:italic>\u03b2<\/jats:italic> (A<jats:italic>\u03b2<\/jats:italic>) peptides at residues 12-28 of A<jats:italic>\u03b2<\/jats:italic> and this binding modulates A<jats:italic>\u03b2<\/jats:italic> accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE\/A<jats:italic>\u03b2<\/jats:italic> interaction with A<jats:italic>\u03b2<\/jats:italic>12-28\u2009P reduced A<jats:italic>\u03b2<\/jats:italic> and tau-related pathology, leading to cognitive improvements in treated AD mice. Recently, we have designed a small peptoid library derived from the A<jats:italic>\u03b2<\/jats:italic>12-28\u2009P sequence to screen for new apoE\/A<jats:italic>\u03b2<\/jats:italic> binding inhibitors with higher efficacy and safety. Peptoids are better drug candidates than peptides due to their inherently more favorable pharmacokinetic properties. One of the lead peptoid compounds, CPO_A<jats:italic>\u03b2<\/jats:italic>17\u201321\u2009P, diminished the apoE\/A<jats:italic>\u03b2<\/jats:italic> interaction and attenuated the apoE4 pro-fibrillogenic effects on A<jats:italic>\u03b2<\/jats:italic> aggregation <jats:italic>in vitro<\/jats:italic> as well as apoE4 potentiation of A<jats:italic>\u03b2<\/jats:italic> cytotoxicity. CPO_A<jats:italic>\u03b2<\/jats:italic>17\u201321\u2009P reduced A<jats:italic>\u03b2<\/jats:italic>-related pathology coupled with cognitive improvements in an AD APP\/PS1 transgenic mouse model. Our study suggests the non-toxic, non-fibrillogenic peptoid CPO_A<jats:italic>\u03b2<\/jats:italic>17\u201321\u2009P has significant promise as a new AD therapeutic agent which targets the A<jats:italic>\u03b2<\/jats:italic> related apoE pathway, with improved efficacy and pharmacokinetic properties.<\/jats:p>","DOI":"10.1038\/s41598-017-08604-8","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T07:30:46Z","timestamp":1502177446000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Targeting Apolipoprotein E\/Amyloid \u03b2 Binding by Peptoid CPO_A\u03b217-21\u2009P Ameliorates Alzheimer\u2019s Disease Related Pathology and Cognitive Decline"],"prefix":"10.1038","volume":"7","author":[{"given":"Shan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Allington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Prelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Mart\u00e1-Ariza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrieta","family":"Scholtzova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goutam","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip B.","family":"Verghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj D.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Uk","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-8966","authenticated-orcid":false,"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"8604_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","volume":"388","author":"P Scheltens","year":"2016","unstructured":"Scheltens, P. et al. 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