Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease.
Alzheimer's disease (AD) manifests with memory loss and spatial disorientation. AD pathology starts in the entorhinal cortex, making it likely that local neural correlates of spatial navigation, particularly grid cells, are impaired. Grid-cell-like representations in humans can be measured using functional magnetic resonance imaging. We found that young adults at genetic risk for AD (APOE-ε4 carriers) exhibit reduced grid-cell-like representations and altered navigational behavior in a virtual arena. Both changes were associated with impaired spatial memory performance. Reduced grid-cell-like representations were also related to increased hippocampal activity, potentially reflecting compensatory mechanisms that prevent overt spatial memory impairment in APOE-ε4 carriers. Our results provide evidence of behaviorally relevant entorhinal dysfunction in humans at genetic risk for AD, decades before potential disease onset.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Department of Epileptology, University of Bonn, Bonn, Germany.
Lukas
L
Kunz
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Tobias Navarro
TN
Schröder
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Hweeling
H
Lee
Department of Psychology, Ulm University, Ulm, Germany.
Christian
C
Montag
Department of Psychology, Ulm University, Ulm, Germany.
Bernd
B
Lachmann
Department of Psychology, Ulm University, Ulm, Germany.
Rayna
R
Sariyska
Department of Psychology, University of Bonn, Bonn, Germany. Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
Martin
M
Reuter
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Rüdiger
R
Stirnberg
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Tony
T
Stöcker
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Department of Epileptology, University of Bonn, Bonn, Germany.
Paul Christian
PC
Messing-Floeter
Department of Epileptology, University of Bonn, Bonn, Germany.
Juergen
J
Fell
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Christian F
CF
Doeller
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Department of Epileptology, University of Bonn, Bonn, Germany. Department of Neuropsychology, Institute of Cognitive Neuroscience, Ruhr-University Bochum, Bochum, Germany. nikolai.axmacher@rub.de.
Nikolai
N
Axmacher
D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D018728:Entorhinal Cortex / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors; D065852:Spatial Memory; D065854:Spatial Navigation; D055815:Young Adult
D053327:Apolipoprotein E4