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@ARTICLE{Lacour:139044,
author = {Lacour, Andre and Espinosa, A. and Louwersheimer, E. and
Heilmann, S. and Hernández, I. and Wolfsgruber, S. and
Fernández, V. and Wagner, H. and Rosende-Roca, M. and
Mauleón, A. and Moreno-Grau, S. and Vargas, L. and
Pijnenburg, Y. A. L. and Koene, T. and Rodríguez-Gómez, O.
and Ortega, G. and Ruiz, S. and Holstege, H. and
Sotolongo-Grau, O. and Kornhuber, J. and Peters, O. and
Frölich, L. and Hüll, M. and Rüther, E. and Wiltfang, J.
and Scherer, M. and Riedel-Heller, S. and Alegret, M. and
Nöthen, M. M. and Scheltens, P. and Tárraga, L. and
Jessen, F. and Boada, M. and Maier, W. and van der Flier, W.
M. and Becker, T. and Ramirez, A. and Ruiz, A.},
title = {{G}enome-wide significant risk factors for {A}lzheimer's
disease: role in progression to dementia due to
{A}lzheimer's disease among subjects with mild cognitive
impairment.},
journal = {Molecular psychiatry},
volume = {22},
number = {1},
issn = {1359-4184},
address = {London},
publisher = {Macmillan},
reportid = {DZNE-2020-05366},
pages = {153-160},
year = {2017},
abstract = {Few data are available concerning the role of risk markers
for Alzheimer's disease (AD) in progression to AD dementia
among subjects with mild cognitive impairment (MCI). We
therefore investigated the role of well-known AD-associated
single-nucleotide polymorphism (SNP) in the progression from
MCI to AD dementia. Four independent MCI data sets were
included in the analysis: (a) the German study on Aging,
Cognition and Dementia in primary care patients (n=853); (b)
the German Dementia Competence Network (n=812); (c) the
Fundació ACE from Barcelona, Spain (n=1245); and (d) the
MCI data set of the Amsterdam Dementia Cohort (n=306). The
effects of single markers and combined polygenic scores were
measured using Cox proportional hazards models and
meta-analyses. The clusterin (CLU) locus was an independent
genetic risk factor for MCI to AD progression (CLU
rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035).
A polygenic score (PGS1) comprising nine established
genome-wide AD risk loci predicted a small effect on the
risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein
E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel
AD loci reported by the International Genomics of
Alzheimer's Project were not implicated in MCI to AD
dementia progression. SNP-based polygenic risk scores
comprising currently available AD genetic markers did not
predict MCI to AD progression. We conclude that SNPs in CLU
are potential markers for MCI to AD progression.},
keywords = {Aged / Aged, 80 and over / Alzheimer Disease: genetics /
Apolipoprotein E4: genetics / Biomarkers / Clusterin:
genetics / Cognitive Dysfunction: genetics / Dementia:
genetics / Disease Progression / Female / Follow-Up Studies
/ Genetic Predisposition to Disease / Genome-Wide
Association Study: methods / Humans / Male / Middle Aged /
Polymorphism, Single Nucleotide: genetics / Risk Factors /
Apolipoprotein E4 (NLM Chemicals) / Biomarkers (NLM
Chemicals) / CLU protein, human (NLM Chemicals) / Clusterin
(NLM Chemicals)},
cin = {AG Becker / AG Wagner / AG Jessen / U Clinical Researchers
- Bonn},
ddc = {610},
cid = {I:(DE-2719)1013007 / I:(DE-2719)1011201 /
I:(DE-2719)1011102 / I:(DE-2719)7000001},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 345 -
Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26976043},
pmc = {pmc:PMC5414086},
doi = {10.1038/mp.2016.18},
url = {https://pub.dzne.de/record/139044},
}