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2022 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

A New Prospect in Triggering Early Hyperexcitability in Alzheimer’s Disease

How may overactive brain cells promote early brain damage in Alzheimer’s?

David Alcantara-Gonzalez, Ph.D.
Nathan Kline Institute
Menands, NY - United States


Nerve cells in the brain use electrical signals to communicate with one another. Such communication is essential for many cognitive functions, including learning and memory. In individuals with Alzheimer’s, however, these electrical signals can become overactive, a phenomenon known as “hyperexcitability”. Recent studies indicate that excessive brain cell activity may contribute to a higher risk of seizures in individuals with Alzheimer’s, especially those in the early stage of disease.

Other studies have found that hyperexcitability may significantly impact a region of the brain called the dentate gyrus, which is important for learning and memory and is vulnerable in early Alzheimer’s. “Mossy cells” are a major type of brain cell in this region, and they normally help turn “on” other cells in the dentate gyrus to promote cognitive abilities. In Alzheimer’s, mossy cells appear to become overly activated and in turn, overstimulate other brain cells. This may hinder dentate gyrus activity and impact dentate gyrus-related learning and memory functions. 

Research Plan

Dr. David Alcantara-Gonzalez and colleagues will study the role of mossy cells in DG hyperexcitability using genetically engineered Alzheimer’s-like mice. They will use electrical recording devices to measure how mossy cell activity may increase in the animals’ brains with Alzheimer’s related brain changes. They will then study the brains of the mice to determine if the overactive mossy cells also experience physical damage, and whether this combination of damage and overstimulation of the mossy cells leads to hyperexcitability in the dentate gyrus. Finally, the researchers will inject the mice with a compound to lower mossy cell activity and study whether this treatment can stop or prevent hyperexcitability in the animals with Alzheimer’s related brain changes. They will also ask whether the reduced overactivity can also reduce other dementia-related factors, such as memory loss and the build-up of Alzheimer’s related brain changes in the brain.  


If successful, this project could shed new light on how hyperexcitability develops and impacts the brain in early-stage Alzheimer’s. They could also identify mossy cells as a target for future dementia therapies.

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