Louwersheimer, Eva, Wolfsgruber, Steffen, Espinosa, Ana ORCID: 0000-0001-8414-6522, Lacour, Andre ORCID: 0000-0003-2692-2583, Heilmann-Heimbach, Stefanie ORCID: 0000-0003-1057-465X, Alegret, Montserrat ORCID: 0000-0002-8164-9500, Hernandez, Isabel, Rosende-Roca, Maitee, Tarraga, Lluis, Boada, Merce, Kornhuber, Johannes ORCID: 0000-0002-8096-3987, Peters, Oliver, Frolich, Lutz ORCID: 0000-0003-1494-0813, Hull, Michael, Ruther, Eckart, Wiltfang, Jens ORCID: 0000-0003-1492-5330, Scherer, Martin, Riedel-Heller, Steffi, Jessen, Frank, Nothen, Markus M., Maier, Wolfgang, Koene, Ted, Scheltens, Philip ORCID: 0000-0002-1046-6408, Holstege, Henne ORCID: 0000-0002-7688-3087, Wagner, Michael ORCID: 0000-0003-2589-6440, Ruiz, Agustin ORCID: 0000-0003-2633-2495, van der Flier, Wiesje M., Becker, Tim and Ramirez, Alfredo ORCID: 0000-0003-4991-763X (2016). Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment. Alzheimers. Dement., 12 (8). S. 872 - 882. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1552-5279

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Abstract

Introduction: We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI). Methods: We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (a beta, tau, ptau). Results: PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (beta +/- SE: 0.24 +/- 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 +/- 0.36, P = 1.21 x 10(-4); ptau: 1.40 +/- 0.36, P = 1.02 x 10(-4)). Discussion: 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-related amyloid deposition. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Louwersheimer, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinosa, AnaUNSPECIFIEDorcid.org/0000-0001-8414-6522UNSPECIFIED
Lacour, AndreUNSPECIFIEDorcid.org/0000-0003-2692-2583UNSPECIFIED
Heilmann-Heimbach, StefanieUNSPECIFIEDorcid.org/0000-0003-1057-465XUNSPECIFIED
Alegret, MontserratUNSPECIFIEDorcid.org/0000-0002-8164-9500UNSPECIFIED
Hernandez, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosende-Roca, MaiteeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarraga, LluisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boada, MerceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kornhuber, JohannesUNSPECIFIEDorcid.org/0000-0002-8096-3987UNSPECIFIED
Peters, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frolich, LutzUNSPECIFIEDorcid.org/0000-0003-1494-0813UNSPECIFIED
Hull, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruther, EckartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDorcid.org/0000-0003-1492-5330UNSPECIFIED
Scherer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedel-Heller, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koene, TedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheltens, PhilipUNSPECIFIEDorcid.org/0000-0002-1046-6408UNSPECIFIED
Holstege, HenneUNSPECIFIEDorcid.org/0000-0002-7688-3087UNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Ruiz, AgustinUNSPECIFIEDorcid.org/0000-0003-2633-2495UNSPECIFIED
van der Flier, Wiesje M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
URN: urn:nbn:de:hbz:38-268642
DOI: 10.1016/j.jalz.2016.01.006
Journal or Publication Title: Alzheimers. Dement.
Volume: 12
Number: 8
Page Range: S. 872 - 882
Date: 2016
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1552-5279
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CEREBROSPINAL-FLUID BIOMARKERS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; CARDIOVASCULAR HEALTH; NATIONAL INSTITUTE; DEMENTIA; LOCI; TAU; GENES; RECOMMENDATIONSMultiple languages
Clinical NeurologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26864

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