Spatial navigation dysfunction could be very early AD warning
medwireNews: The brains of young adults at genetic risk of Alzheimer’s disease (AD) deal with spatial navigation differently from those of people not at risk, a study in Science shows.
The people involved in the study were all young – aged between 18 and 30 years – and healthy, with no neurological symptoms. Yet the researchers found clear differences between at-risk participants with one APOE ε4 allele, and controls homozygous for the ε3 allele.
They therefore suggest that these brain differences may help to determine the optimal time for early intervention, and could act as a prognostic marker.
The area of the brain concerned is the entorhinal cortex, previously identified as a site of very early-onset AD histopathology. The area contains grid cells, the activity of which helps people to understand their position in space and is detectable on functional magnetic resonance imaging.
The 38 at-risk and 37 control participants performed a spatial memory task in which they had to place an item in the correctly recalled location in a virtual environment. The at-risk group had significantly reduced grid-cell activity relative to the control group; nevertheless, their spatial memory was as good as the controls’.
“We assume that the detrimental effect of APOE-ε4 on spatial memory becomes apparent only at older age, when histopathological changes due to presymptomatic AD have reached adjacent limbic regions such as the hippocampus”, say Nikolai Axmacher (German Center for Neurodegenerative Diseases, Bonn) and study co-authors.
However, for all participants, spatial memory performance significantly correlated with grid-cell activity. This paradoxical finding – considering the equivalent performance between two groups with markedly different grid-cell activity – suggested to the team that compensatory mechanisms were at work in the at-risk participants.
The researchers found that lower grid-cell activity correlated with higher hippocampal task-related activity, especially so in the at-risk participants and particularly in the posterior hippocampus, which they say is “especially relevant for spatial navigation”.
In line with this, the at-risk participants spent significantly less time than the controls in the central part of the circular virtual arena, implying that they used the area boundaries to help judge location because they could not rely solely on their internally generated grid representation of the area.
Although this mechanism appeared to fully compensate for the reduced grid-cell activity in the at-risk participants, the team says that the hyperactive hippocampal neurons could later facilitate the spread of amyloid-β aggregation.
“Thus, the increased hippocampal activation may also reflect an adverse condition”, they say.
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