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Due to this finding we sought to understand the possible genetic risk contributed by the\n                    <jats:italic>BACE2<\/jats:italic>\n                    locus to the development of late-onset Alzheimer\u2019s disease (AD). In this study, we report that common single nucleotide polymorphism (SNP) variation in\n                    <jats:italic>BACE2<\/jats:italic>\n                    is associated with altered AD risk in apolipoprotein E gene (APOE) epsilon 4 variant (\u03b54) non-carriers. In addition, in \u03b54 non-carriers diagnosed with AD or mild cognitive impairment (MCI), SNPs within the\n                    <jats:italic>BACE2<\/jats:italic>\n                    locus are associated with cerebrospinal fluid (CSF) levels of A\u03b21-42. Further, SNP variants in\n                    <jats:italic>BACE2<\/jats:italic>\n                    are also associated with BACE2 RNA expression levels suggesting a potential mechanism for the CSF A\u03b21-42 findings. Lastly, overexpression of BACE2\n                    <jats:italic>in vitro<\/jats:italic>\n                    resulted in decreased A\u03b21-40 and A\u03b21-42 fragments in a cell line model of A\u03b2 production. These findings suggest that genetic variation at the\n                    <jats:italic>BACE2<\/jats:italic>\n                    locus modifies AD risk for those individuals who don\u2019t carry the \u03b54 variant of APOE. Further, our data indicate that the biological mechanism associated with this altered risk is linked to amyloid generation or clearance possibly through BACE2 expression changes.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-45896-4","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T06:03:04Z","timestamp":1562133784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Common BACE2 Polymorphisms are Associated with Altered Risk for Alzheimer\u2019s Disease and CSF Amyloid Biomarkers in APOE \u03b54 Non-Carriers"],"prefix":"10.1038","volume":"9","author":[{"given":"Matt","family":"Huentelman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"De Both","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-6005","authenticated-orcid":false,"given":"Wayne","family":"Jepsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio S.","family":"Piras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Talboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Willeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Reiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"45896_CR1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe, D. 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