Universität zu Köln

Lacour, A., Espinosa, A., Louwersheimer, E., Heilmann, S., Hernandez, I., Wolfsgruber, S., Fernandez, V., Wagner, H., Rosende-Roca, M., Mauleon, A., Moreno-Grau, S., Vargas, L., Pijnenburg, Y. A. L., Koene, T., Rodriguez-Gomez, O., Ortega, G., Ruiz, S., Holstege, H., Sotolongo-Grau, O., Kornhuber, J., Peters, O., Froelich, L., Huell, M., Ruether, E., Wiltfang, J., Scherer, M., Riedel-Heller, S., Alegret, M., Noethen, M. M., Scheltens, P., Wagner, M., Tarraga, L., Jessen, F., Boada, M., Maier, W., van der Flier, W. M., Becker, T., Ramirez, A. and Ruiz, A. (2017). Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment. Mol. Psychiatr., 22 (1). S. 153 - 161. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5578

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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 Fundacio 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-e4 (apolipoprotein E-e4) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lacour, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Espinosa, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Louwersheimer, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hernandez, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolfsgruber, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fernandez, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosende-Roca, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauleon, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moreno-Grau, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vargas, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pijnenburg, Y. A. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koene, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodriguez-Gomez, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ortega, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruiz, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holstege, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sotolongo-Grau, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornhuber, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Froelich, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huell, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruether, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiltfang, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riedel-Heller, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alegret, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Noethen, M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheltens, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tarraga, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jessen, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boada, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Flier, W. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruiz, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-243792
DOI:	10.1038/mp.2016.18
Journal or Publication Title:	Mol. Psychiatr.
Volume:	22
Number:	1
Page Range:	S. 153 - 161
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5578
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLASMA CLUSTERIN CONCENTRATION; APOLIPOPROTEIN-E; MYELOID CELLS; COMMON VARIANTS; FOLLOW-UP; ASSOCIATION; GENE; METAANALYSIS; ALLELE; LOCI Multiple languages Biochemistry & Molecular Biology; Neurosciences; Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24379