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However, inheritance of the <jats:italic>APOE<\/jats:italic> \u03b54 allele is not necessary or sufficient for the development of AD. Genetic evidence suggests that multiple loci in a 70\u2009kb region surrounding <jats:italic>APOE<\/jats:italic> are associated with AD risk. Even though these loci could represent surrogate markers in linkage disequilibrium with <jats:italic>APOE<\/jats:italic> \u03b54 allele, they could also contribute biological effects independent of the <jats:italic>APOE<\/jats:italic> \u03b54 allele. Our previous study identified multiple SNPs upstream from <jats:italic>APOE<\/jats:italic> that are associated with cerebrospinal fluid apoE levels, suggesting that a haplotype structure proximal to <jats:italic>APOE<\/jats:italic> can influence apoE expression. In this study, we examined apoE expression in human post\u2010mortem brain (PMB), and constructed chromosome\u2010phase\u2010separated haplotypes of the <jats:italic>APOE<\/jats:italic> proximal region to evaluate their effect on PMB apoE expression. ApoE protein expression was found to differ among AD brain regions and to differ between AD and control hippocampus. In addition, an extended <jats:italic>APOE<\/jats:italic> proximal haplotype structure, spanning from the <jats:italic>TOMM40<\/jats:italic> gene to the <jats:italic>APOE<\/jats:italic> promoter, may modulate apoE expression in a brain region\u2010specific manner and may influence AD disease status. In conclusion, this haplotype\u2013phenotype analysis of apoE expression in PMB suggests that either; (1) the <jats:italic>cis<\/jats:italic>\u2010regulation of <jats:italic>APOE<\/jats:italic> expression levels extends far upstream of the <jats:italic>APOE<\/jats:italic> promoter or (2) an <jats:italic>APOE<\/jats:italic> \u03b54 allele independent mechanism involving the <jats:italic>TOMM40<\/jats:italic> gene plays a role in the risk of AD. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30993","type":"journal-article","created":{"date-parts":[[2009,6,24]],"date-time":"2009-06-24T17:26:17Z","timestamp":1245864377000},"page":"409-417","source":"Crossref","is-referenced-by-count":50,"title":["<i>APOE<\/i> mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure"],"prefix":"10.1002","volume":"153B","author":[{"given":"Lynn 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