While navigating a virtual maze, young adults at high genetic risk of Alzheimer’s disease demonstrated reduced functioning of brain cells involved in spatial navigation, causing them to navigate the maze differently than controls, a new study finds.
Identifying early biomarkers of the disease, such as abnormal grid cell functioning, could be a valuable step in the field of Alzheimer’s research since the best hope for minimizing development of the disease lies in early intervention.
Previous research reveals that Alzheimer’s begins in a region of the brain called the entorhinal cortex (EC) long before symptoms appear; abnormalities can be observed in adults under the age of 30. Lukas Kunz et al. therefore measured the functioning of grid cells, a type of cell in the EC involved in spatial navigation, in young adults navigating a virtual maze.
The researchers compared the performance of individuals with the APOE-ε4 gene, and thus at high risk of developing Alzheimer’s, against control participants.
While the high-risk group had similar spatial memory performance compared to controls, functional magnetic resonance imaging (fMRI) revealed that these individuals had significantly reduced grid cell functioning. This group also showed a reduced preference to navigate in the center of the virtual arena compared to control participants.
Further analysis suggests that the high-risk group may be compensating for their abnormal grid-cell functioning by harnessing the hippocampus, another brain region associated with Alzheimer’s disease, in order to maintain the same level of spatial memory performance seen in the control group.
These differences in grid cell functioning, detectable through simple fMRI, could be used to identify those susceptible to developing Alzheimer’s, although more long-term research is needed to confirm whether early reduced grid-cell functioning is directly related to disease development later in life.
Source: Natasha Pinol – AAAS
Image Credit: Credit: Created by bureaublauwgeel.nl, commissioned by doellerlab.com
Original Research: Abstract for “Reduced grid-cell-like representations in adults at genetic risk for Alzheimer’s disease” by Lukas Kunz, Tobias Navarro Schröder, Hweeling Lee, Christian Montag, Bernd Lachmann, Rayna Sariyska, Martin Reuter, Rüdiger Stirnberg, Tony Stöcker, Paul Christian Messing-Floeter, Juergen Fell, Christian F. Doeller, and Nikolai Axmacher in Science. Published online October 23 2015 doi:10.1126/science.aac8128
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.
“Reduced grid-cell-like representations in adults at genetic risk for Alzheimer’s disease” by Lukas Kunz, Tobias Navarro Schröder, Hweeling Lee, Christian Montag, Bernd Lachmann, Rayna Sariyska, Martin Reuter, Rüdiger Stirnberg, Tony Stöcker, Paul Christian Messing-Floeter, Juergen Fell, Christian F. Doeller, and Nikolai Axmacher in Science. Published online October 23 2015 doi:10.1126/science.aac8128