Reduced grid-cell–like representations in adults at genetic risk for Alzheimer’s disease

Early signs of dementia There is currently no cure for Alzheimer's disease. One of the reasons could be that interventions start too late, when there is already irreversible damage to the brain. Developing a biomarker that would help to effectively start therapy at very early stages of the disease is thus of high interest. Kunz et al. studied neural correlates of spatial navigation in the entorhinal cortex in control study participants and individuals at risk of developing Alzheimer's. The at-risk group showed a different brain signal many decades before the onset of the disease, and they navigated differently in a virtual environment. Science, this issue p. 430 Individuals at risk of developing Alzheimer’s navigate differently in a virtual environment. 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.