Espinosa, Ana ORCID: 0000-0001-8414-6522, Hernandez-Olasagarre, Begona, Moreno-Grau, Sonia, Kleineidam, Luca, Heilmann-Heimbach, Stefanie, Hernandez, Isabel, Wolfsgruber, Steffen, Wagner, Holger, Rosende-Roca, Maitee, Mauleon, Ana, Vargas, Liliana, Lafuente, Asuncion, Rodriguez-Gomez, Octavio, Abdelnour, Carla ORCID: 0000-0002-7636-9758, Gil, Silvia, Marquie, Marta ORCID: 0000-0002-0660-0950, Santos-Santos, Miguel A., Sanabria, Angela, Ortega, Gemma, Monte-Rubio, Gemma, Perez, Alba, Ibarria, Marta, Ruiz, Susana, Kornhuber, Johannes, Peters, Oliver, Froelich, Lutz, Huell, Michael, Wiltfang, Jens, Luck, Tobias ORCID: 0000-0001-7551-4397, Riedel-Heller, Steffi, Montrreal, Laura, Canabate, Pilar ORCID: 0000-0003-4562-8988, Moreno, Mariola, Preckler, Silvia, Aguilera, Nuria, de Rojas, Itziar ORCID: 0000-0002-2148-381X, Orellana, Adelina, Alegret, Montserrat ORCID: 0000-0002-8164-9500, Valero, Sergi, Noethen, Markus M., Wagner, Michael ORCID: 0000-0003-2589-6440, Jessen, Frank, Tarraga, Lluis, Boada, Merce, Ramirez, Alfredo ORCID: 0000-0003-4991-763X and Ruiz, Agustin (2018). Exploring Genetic Associations of Alzheimer's Disease Loci With Mild Cognitive Impairment Neurocognitive Endophenotypes. Front. Aging Neurosci., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1663-4365

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Abstract

The role of genetic risk markers for Alzheimer's disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundacio ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-epsilon 4 was significantly associated with the memory function NEs delayed recall (DR) (beta = -0.76, p = 4.1 x 10(-10)), learning (beta = -1.35, p = 2.91 x 10(-6)), and recognition memory (beta = -0.58, p = 9.67 x 10(-5)); and with DR in the aMCI group (beta = -0.36, p = 2.96 x 10(-5)). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-epsilon 4 was also significantly associated with the NE learning in individuals classified as having Pss-aMCI (beta = -1.37, p = 5.82 x 10(-5)). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the backward digits working memory NE (beta = -0.52, p = 7.57 x 10(-5)) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE repetition (beta = -0.19, p = 5.34 x 10(-6)). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Espinosa, AnaUNSPECIFIEDorcid.org/0000-0001-8414-6522UNSPECIFIED
Hernandez-Olasagarre, BegonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreno-Grau, SoniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleineidam, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilmann-Heimbach, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosende-Roca, MaiteeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauleon, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vargas, LilianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lafuente, AsuncionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Gomez, OctavioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdelnour, CarlaUNSPECIFIEDorcid.org/0000-0002-7636-9758UNSPECIFIED
Gil, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marquie, MartaUNSPECIFIEDorcid.org/0000-0002-0660-0950UNSPECIFIED
Santos-Santos, Miguel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanabria, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortega, GemmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monte-Rubio, GemmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez, AlbaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ibarria, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruiz, SusanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kornhuber, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froelich, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huell, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luck, TobiasUNSPECIFIEDorcid.org/0000-0001-7551-4397UNSPECIFIED
Riedel-Heller, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montrreal, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canabate, PilarUNSPECIFIEDorcid.org/0000-0003-4562-8988UNSPECIFIED
Moreno, MariolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preckler, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aguilera, NuriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Rojas, ItziarUNSPECIFIEDorcid.org/0000-0002-2148-381XUNSPECIFIED
Orellana, AdelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alegret, MontserratUNSPECIFIEDorcid.org/0000-0002-8164-9500UNSPECIFIED
Valero, SergiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarraga, LluisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boada, MerceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Ruiz, AgustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-168925
DOI: 10.3389/fnagi.2018.00340
Journal or Publication Title: Front. Aging Neurosci.
Volume: 10
Date: 2018
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 1663-4365
Language: English
Faculty: Faculty of Management, Economy and Social Sciences
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
APOE EPSILON-4 ALLELE; DIFFERENTIAL-DIAGNOSIS; MEMORY DECLINE; RISK VARIANTS; FOLLOW-UP; AGE; DEMENTIA; INDIVIDUALS; GENOTYPE; PERFORMANCEMultiple languages
Geriatrics & Gerontology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16892

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