Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
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...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 2016
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| In: |
Alzheimer's and dementia
Year: 2016, Jahrgang: 12, Heft: 8, Pages: 872-881 |
| ISSN: | 1552-5279 |
| DOI: | 10.1016/j.jalz.2016.01.006 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1016/j.jalz.2016.01.006 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1552526016000467 
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| Verfasserangaben: | Eva Louwersheimer, Steffen Wolfsgruber, Ana Espinosa, André Lacour, Stefanie Heilmann-Heimbach, Montserrat Alegret, Isabel Hernández, Maitée Rosende-Roca, Lluís Tárraga, Mercè Boada, Johannes Kornhuber, Oliver Peters, Lutz Frölich, Michael Hüll, Eckart Rüther, Jens Wiltfang, Martin Scherer, Steffi Riedel-Heller, Frank Jessen, Markus M. Nöthen, Wolfgang Maier, Ted Koene, Philip Scheltens, Henne Holstege, Michael Wagner, Agustín Ruiz, Wiesje M. van der Flier, Tim Becker, Alfredo Ramirez |
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| 245 | 1 | 0 | |a Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment |c Eva Louwersheimer, Steffen Wolfsgruber, Ana Espinosa, André Lacour, Stefanie Heilmann-Heimbach, Montserrat Alegret, Isabel Hernández, Maitée Rosende-Roca, Lluís Tárraga, Mercè Boada, Johannes Kornhuber, Oliver Peters, Lutz Frölich, Michael Hüll, Eckart Rüther, Jens Wiltfang, Martin Scherer, Steffi Riedel-Heller, Frank Jessen, Markus M. Nöthen, Wolfgang Maier, Ted Koene, Philip Scheltens, Henne Holstege, Michael Wagner, Agustín Ruiz, Wiesje M. van der Flier, Tim Becker, Alfredo Ramirez |
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| 520 | |a 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 (aβ, tau, ptau). - Results - PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± 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. | ||
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a Endophenotypes | |
| 650 | 4 | |a Genetic risk variants | |
| 650 | 4 | |a Mild cognitive impairment | |
| 650 | 4 | |a Polygenic risk score | |
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