Cover Image

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Louwersheimer, Eva (Author) , Frölich, Lutz (Author)
Format: Article (Journal)
Language:English
Published: August 2016
In: Alzheimer's and dementia
Year: 2016, Volume: 12, Issue: 8, Pages: 872-881
ISSN:1552-5279
DOI:10.1016/j.jalz.2016.01.006
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.jalz.2016.01.006
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1552526016000467
Get full text
Author Notes: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
Description
Summary: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.
Item Description:Gesehen am 09.08.2019
Physical Description:Online Resource
ISSN:1552-5279
DOI:10.1016/j.jalz.2016.01.006

Similar Items