Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment

Journal article

Publication Details

Author(s): Louwersheimer E, Wolfsgruber S, Espinosa A, Lacour A, Heilmann-Heimbach S, Alegret M, Hernandez I, Rosende-Roca M, Tarraga L, Boada M, Kornhuber J, Peters O, Frolich L, Hull M, Ruther E, Wiltfang J, Scherer M, Riedel-Heller S, Jessen F, Nothen MM, Maier W, Koene T, Scheltens P, Holstege H, Wagner M, Ruiz A, Van Der Flier WM, Becker T, Ramirez A
Journal: Alzheimers & Dementia
Publication year: 2016
Volume: 12
Journal issue: 8
Pages range: 872-81
ISSN: 1552-5260


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).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?, tau, ptau).PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (? ± SE:-0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10(-4); ptau: 1.40 ± 0.36, P = 1.02 × 10(-4)).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.

FAU Authors / FAU Editors

Kornhuber, Johannes Prof. Dr. med.
Lehrstuhl für Psychiatrie und Psychotherapie

External institutions with authors

Albert-Ludwigs-Universität Freiburg
Charité - Universitätsmedizin Berlin
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Fundació ACE: Barcelona Alzheimer Treatment and Research Center
Georg-August-Universität Göttingen
Rheinische Friedrich-Wilhelms-Universität Bonn
Ruprecht-Karls-Universität Heidelberg
Universität Greifswald
Universität Köln
Universität Leipzig
Universitätsklinikum Hamburg-Eppendorf (UKE)
Vrije Universiteit Amsterdam (VU) / University Amsterdam

How to cite

Louwersheimer, E., Wolfsgruber, S., Espinosa, A., Lacour, A., Heilmann-Heimbach, S., Alegret, M.,... Ramirez, A. (2016). Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment. Alzheimers & Dementia, 12(8), 872-81.

Louwersheimer, Eva, et al. "Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment." Alzheimers & Dementia 12.8 (2016): 872-81.


Last updated on 2018-07-10 at 02:26