Apolipoprotein E Homozygous ε4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure

THEORETICAL BACKGROUND: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated w...

Authors: Goltermann, Janik
Redlich, Ronny
Dohm, Katharina
Zaremba, Dario
Repple, Jonathan
Kaehler, Claas
Grotegerd, Dominik
Förster, Katharina
Meinert, Susanne
Enneking, Verena
Schlaghecken, Emily
Fleischer, Lara
Hahn, Tim
Kugel, Harald
Jansen, Andreas
Krug, Axel
Brosch, Katharina
Nenadic, Igor
Schmitt, Simon
Stein, Frederike
Meller, Tina
Yüksel, Dilara
Fischer, Elena
Rietschel, Marcella
Witt, Stephanie
Forstner, Andreas Josef
Nöthen, Markus Maria
Kircher, Tilo
Thalamuthu, Anbupalam
Baune, Bernhard Th.
Dannlowski, Udo
Opel, Nils
Division/Institute:FB 05: Medizinische Fakultät
FB 07: Psychologie und Sportwissenschaft
Document types:Article
Media types:Text
Publication date:2019
Date of publication on miami:18.02.2020
Modification date:18.02.2020
Edition statement:[Electronic ed.]
Source:Frontiers in Neurology 10 (2019) 52, 552, 1-11
Subjects:apolipoprotein E; visuospatial working memory; cognitive deficits; hippocampus, structural MRI; Alzheimer; major depression
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
The FOR 2107 consortium is supported by the German Research Council (Deutsche Forschungsgemeinschaft, DFG, Grant nos. KI 588/14-1, KI 588/14-2, KR 3822/7-1, KR 3822/7-2, NE 2254/1-2, DA 1151/5-1, DA 1151/5-2, SCHW 559/14-1, 545/7-2, RI 908/11-2, WI 3439/3-2, NO 246/10-2, DE 1614/3-2, HA 7070/2-2, JA 1890/7-1, JA 1890/7-2, MU 1315/8-2, RE 737/20-2, KI 588/17-1).
This work was furthermore funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the Medical Faculty of Münster (grant Dan3/012/17 to UD).
Format:PDF document
URN:urn:nbn:de:hbz:6-92119421918
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-92119421918
Other Identifiers:DOI: 10.3389/fneur.2019.00552
Digital documents:artikel_dannlowski_2019.pdf

THEORETICAL BACKGROUND: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. METHODS: A sample of n = 31 homozygous ε4 carriers was contrasted with n = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ε4 carriers and n = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. RESULTS: Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. CONCLUSION: Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.