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Study: Early Alzheimer's Clues Appear In The Brain's Internal GPS

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Alzheimer’s researchers have uncovered a surprising clue linked to whether someone is likely to develop the disease later in life. A study published in the latest issue of Science finds that the brains of people at greatest genetic risk of developing Alzheimer's show less activity in a network of neurons that serve as our internal navigation system – known as “grid cells.”

The discovery of brain cells devoted to navigation is itself extremely new, winning its discoverers the 2014 Nobel Prize in Physiology or Medicine. These specialized neurons form a grid structure within a brain region called the entorhinal cortex that plays a major role in memory and navigation. As we move around, the grid activates like an internal GPS, tracking our movements and creating mental maps that allow us to navigate without visual cues. The reason you can close your eyes and still eventually find your way around a room is a result of your grid cells mapping your movements.

Prior research has found that people carrying a variant of the gene linked to developing Alzheimer’s (known as APOE-e4) are also at greatest risk of developing abnormalities in their entorhinal cortex. So researchers wondered if they could find a link between the presence of the Alzheimer’s gene and reduced activity in the brain region’s grid cells.

The study included two groups of young adults—one carrying the Alzheimer’s gene variant, one without it—neither of which showed symptoms of the disease. The participants were asked to navigate a virtual space (a large circular area with blue sky and mountains in the distance) while completing simple tasks like picking up basketballs and returning them to the same place later in the experiment. As the participants completed these navigational tasks, the researchers monitored their brain activity with fMRI.

As suspected, brains of the participants carrying the Alzheimer’s gene variant showed less activity in their grid cell networks compared to the other group. Strangely, though, both groups performed equally well with the virtual arena tasks, although the way the groups navigated the space was different. The group with less grid cell activity tended to stay along the edges of the virtual space, while the other group used the entire space to navigate.

The fMRI scan also showed an uptick of activity in the hippocampus—a brain region near the entorhinal cortex that plays a role in memory formation—in the brains of participants with less grid cell activity, which seems to indicate that their brains recruited the hippocampus to help with navigation. “This suggests that you can either use the grid cell system or you can use the hippocampus,” according to neuroscientist Nikolai Axmacher, one of the study’s authors, as reported in Science.

A few important implications fall out of this study. First, the grid cell network may be a new window into understanding early stages of Alzheimer’s development, providing researchers clues as to how treatment could be delivered earlier in life before the disease causes irreparable damage. Finding these early-stage clues has proven extremely difficult and the pressure is on researchers to uncover more of them. An additional implication is a better understanding of the spatial disorientation that accompanies the onset of Alzheimer's, which could lead to more effective treatment therapies addressing that aspect of the disease.

The study was published in Science.

You can find David DiSalvo on Twitter @neuronarrative and at his website daviddisalvo.org.

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