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It is caused by a combination of a subject\u2019s heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer\u2019s disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers. A JASPAR database search predicts that the T to C transition in rs429358 generates a binding motif for nuclear respiratory factor NRF1. This site appears to be part of a binding site cluster for this transcription factor on exon 4 of APOE. This <jats:italic>de novo<\/jats:italic> NRF1 binding site has therefore the potential to affect the expression of multiple genes in its genomic vicinity. Our <jats:italic>in silico<\/jats:italic> analysis, suggesting a novel function for APOE4 at the DNA level, offers a potential mechanism for the observed tissue specific neurodegeneration and the role of environmental factors in Alzheimer\u2019s disease etiology.<\/jats:p>","DOI":"10.1038\/srep40668","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T15:15:12Z","timestamp":1484666112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of a Nuclear Respiratory Factor 1 Recognition Motif in the Apolipoprotein E Variant APOE4 linked to Alzheimer\u2019s Disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Anne","family":"Urfer-Buchwalder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Urfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"BFsrep40668_CR1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/aje\/155.6.487","volume":"155","author":"JE Eichner","year":"2002","unstructured":"Eichner, J. 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