Because Alzheimer’s disease is a progressive disorder, scientists are looking to clarify the brain changes that occur in the disease’s earliest stage, when therapies can be most effective. These early changes include the clumping of protein molecules called beta-amyloid and tau in the temporal lobe — a brain region key to learning and memory. Research has also found that people with early Alzheimer’s experience spatial disorientation, or the inability to recognize places and find their way from one location to another, even in familiar environments such as a neighborhood or home. While scientists do not know exactly how spatial disorientation develops in early Alzheimer’s disease, evidence suggests that it may involve damage to certain brain cells called “head-direction” cells. These are cell that become activated when an animal points its head in a particular direction suggesting their importance in spatial orientation. However, damage to head-direction cells may induce spatial disorientation and possibly play a role in the development of dementia.

Benjamin Clark, Ph.D., and colleagues plan to test the hypothesis that spatial disorientation in early Alzheimer’s disease is due in part to an impaired head-direction cell system. For this effort, they will use a novel rat model engineered to develop beta-amyloid, tau, and other Alzheimer’s-related brain changes. They will assess whether the mice develop changes to the structure and activity of their head-direction cells, and whether these changes are associated with poor performance on spatial orientation tasks. Such work will involve sophisticated techniques for imaging brain cells and recording electrical cellular function from this network of cells. 

The results of this effort, if successful, could lead to a greater understanding of the mechanism responsible for spatial disorientation in humans and the development of dementia. Ultimately, this network of cells could play an important role in early detection and treating Alzheimer’s disease.