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Cerebral Cortex Advance Access originally published online on October 31, 2006
Cerebral Cortex 2007 17(8):1934-1947; doi:10.1093/cercor/bhl103
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Better Memory and Neural Efficiency in Young Apolipoprotein E {varepsilon}4 Carriers

Christian R. A. Mondadori1, Dominique J. -F. de Quervain1, Andreas Buchmann1, Henrietta Mustovic1, M. Axel Wollmer1, Conny F. Schmidt2, Peter Boesiger2, Christoph Hock1, Roger M. Nitsch1, Andreas Papassotiropoulos1 and Katharina Henke3

1 Division of Psychiatry Research, University of Zurich, 8032 Zurich, Switzerland, 2 Institute for Biomedical Engineering, University and ETH Zurich, 8092 Zurich, Switzerland, 3 Institute of Psychology, University of Bern, 3000 Bern 9, Switzerland

Address correspondence to Katharina Henke, Institute of Psychology, University of Bern, Muesmattstrasse 9, 3000 Bern 9, Switzerland. Email: henke{at}psy.unibe.ch.

The apolipoprotein E (APOE) {varepsilon}4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE {varepsilon}4 with better episodic memory compared with APOE {varepsilon}2 and {varepsilon}3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas {varepsilon}2 and {varepsilon}3 carriers increased activity. This smaller neural investment of {varepsilon}4 carriers into learning reappeared during retrieval: {varepsilon}4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE {varepsilon}4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.

Key Words: Alzheimer's disease • APOE gene • functional magnetic resonance imaging • hippocampus • learning • neuroimaging


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