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Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to \u201ccoordinated lysosomal expression and regulation\u201d (CLEAR) DNA motifs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by <jats:italic>APOE<\/jats:italic> genotype and in a glioblastoma cell line expressing either apoE3 or apoE4. Computational modeling assessed interactions between apoE and mutated apoE with CLEAR or modified DNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three TFEB\u2010regulated mRNA transcripts\u2014<jats:italic>SQSTM, MAP1LC3B<\/jats:italic>, and <jats:italic>LAMP2<\/jats:italic>\u2014were lower in AD \u025b4\/\u025b4 than in AD \u025b3\/\u025b3 brains. Computational modeling predicted avid specific binding of apoE4 to CLEAR motifs. ApoE was found in cellular nuclei, and in\u00a0vitro binding assays suggest competition between apoE4 and TFEB at CLEAR sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ApoE4\u2010CLEAR interactions may account for suppressed autophagy in <jats:italic>APOE<\/jats:italic> \u025b4\/\u025b4 carriers and, in this way, contribute to earlier AD onset.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2017.07.754","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T23:32:05Z","timestamp":1506123125000},"page":"230-242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs"],"prefix":"10.1002","volume":"14","author":[{"given":"Paul A.","family":"Parcon","sequence":"first","affiliation":[{"name":"Donald W. 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