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2020 Alzheimer's Association Research Grant (AARG)

Elucidation of Early Circuit Dysfunction in Alzheimer's Disease Pathogenesis

Could understanding brain changes at the earliest stages of Alzheimer’s uncover novel targets for therapy development?

Kevin Beier, Ph.D.
University of California
Irvine, CA - United States



Background

Recent studies suggest that brain changes associated with Alzheimer’s can occur decades before outward symptoms appear. Studies show that some nerve cells are more vulnerable to these brain changes than others. However, it is not entirely clear which kinds of nerve cells in the brain are the first to be impacted in Alzheimer’s, or how this may impact broader nerve cell networks, or “circuits", in the brain.

Dr. Kevin Beier and colleagues have developed a technique to track nerve cell network activity in the brains of mice. The technique uses a combination of manipulations to track changes in nerve cell network activity as they occur.
 

Research Plan

Dr. Beier’s team will use a novel technique that they have developed to identify nerve cell circuits that undergo significant changes during Alzheimer’s progression. The researchers will study two different models of genetically engineered Alzheimer’s-like mice to conduct their studies; each model may have its benefits as well as limitations. Using these mouse models, Dr. Beier and colleagues will track changes in nerve cell network activity during throughout the brain during disease progression. For the second part of their study, the researchers will target the nerve cell networks they identified in their initial experiments and artificially modulate the network activity, and determine if they can delay, or slow development of behavioral and cognitive symptoms associated with Alzheimer’s.

Impact

This study may provide deeper insights into brain changes that occur during the earliest stages of Alzheimer’s, before cognitive symptoms appear. It could reveal nerve cell networks that may be suitable for novel therapy approaches and could give rise to potential treatments for Alzheimer’s.

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