Journal Article

DZNE-2020-05018

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment.

Louwersheimer, E. (Corresponding author) ; Wolfsgruber, S.DZNE* ; Espinosa, A. ; Lacour, A.DZNE* ; Heilmann-Heimbach, S. ; Alegret, M. ; Hernández, I. ; Rosende-Roca, M. ; Tárraga, L. ; Boada, M. ; Kornhuber, J. ; Peters, O. ; Frölich, L. ; Hüll, M. ; Rüther, E. ; Wiltfang, J. ; Scherer, M. ; Riedel-Heller, S. ; Jessen, F. ; Nöthen, M. M. ; Maier, W.DZNE* ; Koene, T. ; Scheltens, P. ; Holstege, H. ; Wagner, M.DZNE* ; Ruiz, A. ; van der Flier, W. M. ; Becker, T. ; Ramirez, A.

2016
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jalz.2016.01.006

Abstract: 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.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Apolipoproteins E: genetics (MeSH) ; Cognitive Dysfunction: cerebrospinal fluid (MeSH) ; Cognitive Dysfunction: complications (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Cohort Studies (MeSH) ; Datasets as Topic: statistics & numerical data (MeSH) ; Endophenotypes: cerebrospinal fluid (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Mental Status Schedule (MeSH) ; Middle Aged (MeSH) ; Multifactorial Inheritance: genetics (MeSH) ; Neuropsychological Tests (MeSH) ; Odds Ratio (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Statistics, Nonparametric (MeSH) ; Amyloid beta-Peptides ; Apolipoproteins E

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Contributing Institute(s):

1. Neuropsychology (AG Wagner)
2. GenomMathematik in der Neuroepidemiologie (AG Becker ; GenomMathematik ; GenomMathematik)
3. U Clinical Researchers - Bonn (U Clinical Researchers - Bonn)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2016

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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