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Weighted polygenic risk scores (PGS) were constructed of 18 non\u2010apolipoprotein E (<jats:italic>APOE<\/jats:italic>) AD risk variants. In addition, we determined <jats:italic>APOE<\/jats:italic> genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (a\u03b2, tau, ptau).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PGS was modestly associated with cognitive decline over time, as measured by mini\u2010mental state examination (MMSE) (\u03b2 \u00b1 SE:\u22120.24 \u00b1 0.10; <jats:italic>P<\/jats:italic> = .012), and with CSF levels of tau and ptau (tau: 1.38 \u00b1 0.36, <jats:italic>P<\/jats:italic> = 1.21 \u00d7 10<jats:sup>\u22124<\/jats:sup>; ptau: 1.40 \u00b1 0.36, <jats:italic>P<\/jats:italic> = 1.02 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer\u2010related amyloid deposition.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2016.01.006","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T06:15:13Z","timestamp":1456467313000},"page":"872-881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment"],"prefix":"10.1002","volume":"12","author":[{"given":"Eva","family":"Louwersheimer","sequence":"first","affiliation":[{"name":"Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam VU University Medical Centre  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Wolfsgruber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University of Bonn  Bonn Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Alzheimer Research Center and Memory Clinic of Fundaci\u00f3 ACE Institut Catal\u00e0 de Neuroci\u00e8ncies Aplicades  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Lacour","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Heilmann\u2010Heimbach","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn  Bonn Germany"},{"name":"Department of Genomics, Life &amp; 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