학술논문
Genome-wide significant risk factors for Alzheimerʼs disease: role in progression to dementia due to Alzheimerʼs disease among subjects with mild cognitive impairment
Document Type
Academic Journal
Author
Lacour, A; Espinosa, A; Louwersheimer, E; Heilmann, S; Hernández, I; Wolfsgruber, S; Fernández, V; Wagner, H; Rosende-Roca, M; Mauleón, A; Moreno-Grau, S; Vargas, L; Pijnenburg, Y AL; Koene, T; Rodríguez-Gómez, O; Ortega, G; Ruiz, S; Holstege, H; Sotolongo-Grau, O; Kornhuber, J; Peters, O; Frölich, L; Hüll, M; Rüther, E; Wiltfang, J; Scherer, M; Riedel-Heller, S; Alegret, M; Nöthen, M M; Scheltens, P; Wagner, M; Tárraga, L; Jessen, F; Boada, M; Maier, W; van der Flier, W M; Becker, T; Ramirez, A; Ruiz, A
Source
Molecular Psychiatry. Jan 01, 2017 22(1):153-160
Subject
Language
English
ISSN
1359-4184
Abstract
Few data are available concerning the role of risk markers for Alzheimerʼs 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-ε4 (apolipoprotein E-ε4) carriers (HR = 1.746 (1.029-2.965); P = 0.038). The novel AD loci reported by the International Genomics of Alzheimerʼs 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.