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Spatial navigation abnormalities could hint at Alzheimer's years before onset

American Association for the Advancement of Science

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IMAGE: Genetic risk for Alzheimer's disease is linked to reduced grid-cell-like representations during virtual navigation. view more

Credit: [Credit: Created by bureaublauwgeel.nl, commissioned by doellerlab.com]

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.

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Article #9: "Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease," by L. Kunz; H. Lee; R. Stirnberg; T. Stöcker; P.C. Messing-Floeter; N. Axmacher at German Center for Neurodegenerative Diseases (DZNE) in Bonn, Germany; L. Kunz; M. Reuter; P.C. Messing-Floeter; J. Fell at University of Bonn in Bonn, Germany; T.N. Schröder; C.F. Doeller at Radboud University in Nijmegen, Netherlands; C. Montag; B. Lachmann; R. Sariyska at Ulm University in Ulm, Germany; N. Axmacher at Ruhr-University Bochum in Bochum, Germany.

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