Early Alzheimer’s Biomarker May Exist in Young at High Genetic Risk of Disease

A research team attempting to identify new biomarkers of Alzheimer’s disease has found that young subjects at high genetic risk of Alzheimer’s development — while moving through a virtual maze — showed lower brain cell activity involved in spatial navigation than a control group, revealing differences in the brain decades before possible disease onset. The study, entitled “Reduced grid-cell–like representations in adults at genetic risk for Alzheimer’s disease,” was published in Science.

Memory loss and spatial disorientation are common symptoms of Alzheimer’s disease (AD). Previous research has shown that AD pathogenesis starts in a region of the brain called entorhinal cortex (EC), where grid cells, the types of neurons involved in spatial representation and navigation, are located.

Researchers studied young individuals who carried the APOE-ε4 gene, a genetic factor associated with both a higher risk of developing the disease and early AD onset. The control group and the high-risk group were both subjected to a virtual arena. The navigation patterns observed suggest similar memory navigating performances in the two groups, but functional magnetic resonance imaging (fMRI) in the high-risk group showed significantly reduced grid cell functioning and these individuals also had a tendency to navigate the virtual maze in the center, a behavior not observed in control participants.

Subsequent analysis, researchers said, suggest that the high-risk group’s preference for navigating from the center was a form of compensation for the lower grid-cell function through increased hippocampal activity (the hippocampus being another brain region associated with AD), which allowed them to maintain a similar level of performance and spatial memory as the control group.

“Our results provide evidence of behaviorally relevant entorhinal dysfunction in humans at genetic risk for AD, decades before potential disease onset,” the researchers concluded.

The behavioral differences and grid-cell dysfunction observed in those with increased genetic risk, detectable through fMRI, represent a potential disease biomarker for identifying people susceptible to developing Alzheimer’s disease. These promising results, however, need further study to determine if a direct correlation exists between observed early reductions in grid cell function and the later onset of Alzheimer’s disease, the researchers concluded.

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