Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Alzheimers Dement. 2016 Aug;12(8):872-81. doi: 10.1016/j.jalz.2016.01.006. Epub 2016 Feb 26.

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

Author information

1
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: e.louwersheimer@vumc.nl.
2
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
3
Alzheimer Research Center and Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
4
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
5
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
6
Department of Psychiatry and Psychotherapy, University Clinic Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
7
Department of Psychiatry, Charité University Medicine, Berlin, Germany.
8
Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
9
Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, Freiburg, Germany.
10
Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
11
Department of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
12
Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
13
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
14
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Alzheimer Center and Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.
15
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
16
Alzheimer Center and Department of Clinical Genetics, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
17
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
18
Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
19
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany. Electronic address: alfredo.ramirez@ukb.uni-bonn.de.

Abstract

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 × 10(-4); ptau: 1.40 ± 0.36, P = 1.02 × 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.

KEYWORDS:

Alzheimer's disease; Endophenotypes; Genetic risk variants; Mild cognitive impairment; Polygenic risk score

PMID:
26921674
DOI:
10.1016/j.jalz.2016.01.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center