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An extra copy of or gain-of-function mutations in APP correlate with early onset AD. Compared to the other variants (APOE2 and APOE3), the \u03b54 allele of APOE (APOE4) hastens and exacerbates early and late onset forms of AD. Convenient in vivo models to study how APP and APOE4 interact at the cellular and molecular level to influence neurodegeneration are lacking. Here, we show that the nematode C. elegans can model important aspects of AD including age-related, patterned neurodegeneration that is exacerbated by APOE4. Specifically, we found that APOE4, but not APOE3, acts with APP to hasten and expand the pattern of cholinergic neurodegeneration caused by APP. Molecular mechanisms underlying how APP and APOE4 synergize to kill some neurons while leaving others unaffected may be uncovered using this convenient worm model of neurodegeneration.<\/jats:p>","DOI":"10.1534\/g3.120.401486","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T22:45:11Z","timestamp":1593038711000},"page":"2851-2861","source":"Crossref","is-referenced-by-count":14,"title":["<i>APP<\/i>\n                    -Induced Patterned Neurodegeneration Is Exacerbated by\n                    <i>APOE4<\/i>\n                    in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1093","volume":"10","author":[{"given":"Wisath","family":"Sae-Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa L","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotti","family":"Brose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliyah J","family":"Encarnacion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragati","family":"Kore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lashaun O","family":"Oyibo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K","family":"Rozmiarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan T","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"2021042011141046100_bib1","doi-asserted-by":"publisher","DOI":"10.3908\/wormatlas.1.17"},{"key":"2021042011141046100_bib2","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1126\/science.1178343","article-title":"Starvation protects germline stem cells and extends reproductive longevity in C. elegans.","volume":"326","author":"Angelo","year":"2009","journal-title":"Science"},{"key":"2021042011141046100_bib3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.bbr.2016.06.035","article-title":"Conserved regulators of cognitive aging: From worms to humans.","volume-title":"Behav Brain Res","author":"Arey","year":"2017"},{"key":"2021042011141046100_bib4","doi-asserted-by":"publisher","first-page":"6771","DOI":"10.1523\/JNEUROSCI.0887-09.2009","article-title":"Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice.","volume":"29","author":"Bales","year":"2009","journal-title":"J. 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