<< Back

2024 Alzheimer's Association Research Grant (AARG)

Ventral Hippocampal Circuitry Underlying Neuropsychiatric Symptoms in AD

Can abnormal activity in a brain region involved in learning and memory help explain the link between anxiety and dementia risk?

Holly Hunsberger, Ph.D.
Rosalind Franklin University of Medicine and Science
North Chicago, IL - United States


Alzheimer’s disease gets worse over time and can begin decades before clinical symptoms become evident. As such, scientists are looking for novel ways to diagnose the disease at its earliest stages, when disease treatments can be most effective. One area of research has involved studying links between dementia and neuropsychiatric symptoms, such as depression and anxiety. People with Alzheimer’s often experience these symptoms during the disease, but recent evidence indicates that anxiety can predict the development of Alzheimer’s at an early stage. Research has also found that women, who represent nearly two-thirds of Americans living with Alzheimer’s, are more susceptible to depression and anxiety. Such findings suggest the need to further study how anxiety and Alzheimer’s are related in men and women, and whether this relationship may reveal how memory loss and other forms of cognitive decline in the disease begin. 

In preliminary studies with Alzheimer’s-like mice, Dr. Holly C. Hunsberger and colleagues found that female mice show cognitive decline earlier than male mice. They also found that memory impairment is linked to anxiety only in female mice. To better understand this link, the researchers observed nerve cell activity in the ventral CA1 (vCA1), a part of a brain region that is important for learning and memory. They found that certain nerve cell activity in this sub-region was abnormally increased in female mice experiencing anxiety-like behavior. Overactive nerve cells, a phenomenon known as “hyperexcitability,” may be linked to cognitive decline in Alzheimer’s. 

Research Plan

Dr. Hunsberger and the team will now conduct a larger study of anxiety and ventral C1 activity in Alzheimer’s. For their effort, they will inject a specific “highlighting” compound, as well as a lens, into the vCA1 of male and female Alzheimer’s-like mice. This procedure will enable them to see minute changes in vCA1 nerve cell activity over time. First, Dr. Hunsberger’s team will expose the mice to anxiety-inducing exercises, and then assess how this exposure impacts vCA1 nerve cell activity and memory in the male and female animals. Next, the mice will be injected with another highlighting compound that will enable the team to identify particular nerve cell networks in the vCA1 that drive anxiety-like behavior in the mice. Lastly, Dr. Hunsberger’s team will inject compounds into two other brain regions of their mice, the basal amygdala and the lateral hypothalamus. These regions are involved in anxiety behavior, and the compounds are designed to either stop or activate brain activity linked to such behavior. The researchers will then assess how the compounds may prevent or exacerbate vCA1 brain cell activity and memory loss in the animals. 


Results from this study could help clarify the biological mechanisms linking anxiety and dementia in men and women. They could also identify anxiety-related mechanisms in brain circuitry that may be used as targets for future dementia therapies.

Back to Top