TY  - JOUR
AU  - Louwersheimer, Eva
AU  - Wolfsgruber, Steffen
AU  - Espinosa, Ana
AU  - Lacour, André
AU  - Heilmann-Heimbach, Stefanie
AU  - Alegret, Montserrat
AU  - Hernández, Isabel
AU  - Rosende-Roca, Maitée
AU  - Tárraga, Lluís
AU  - Boada, Mercè
AU  - Kornhuber, Johannes
AU  - Peters, Oliver
AU  - Frölich, Lutz
AU  - Hüll, Michael
AU  - Rüther, Eckart
AU  - Wiltfang, Jens
AU  - Scherer, Martin
AU  - Riedel-Heller, Steffi
AU  - Jessen, Frank
AU  - Nöthen, Markus M
AU  - Maier, Wolfgang
AU  - Koene, Ted
AU  - Scheltens, Philip
AU  - Holstege, Henne
AU  - Wagner, Michael
AU  - Ruiz, Agustín
AU  - van der Flier, Wiesje M
AU  - Becker, Tim
AU  - Ramirez, Alfredo
TI  - Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment.
JO  - Alzheimer's and dementia
VL  - 12
IS  - 8
SN  - 1552-5260
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2020-05018
SP  - 872-881
PY  - 2016
AB  - 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 (aβ, tau, ptau).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 × 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.
KW  - Aged
KW  - Aged, 80 and over
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Alzheimer Disease: diagnosis
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Apolipoproteins E: genetics
KW  - Cognitive Dysfunction: cerebrospinal fluid
KW  - Cognitive Dysfunction: complications
KW  - Cognitive Dysfunction: genetics
KW  - Cohort Studies
KW  - Datasets as Topic: statistics & numerical data
KW  - Endophenotypes: cerebrospinal fluid
KW  - Female
KW  - Humans
KW  - Male
KW  - Mental Status Schedule
KW  - Middle Aged
KW  - Multifactorial Inheritance: genetics
KW  - Neuropsychological Tests
KW  - Odds Ratio
KW  - Polymorphism, Single Nucleotide: genetics
KW  - Statistics, Nonparametric
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Apolipoproteins E (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26921674
DO  - DOI:10.1016/j.jalz.2016.01.006
UR  - https://pub.dzne.de/record/138696
ER  -