2023 Alzheimer's Association Research Grant (AARG)

Targeting KCC2 for rescuing functional impairments in Alzheimer's disease

Can increasing the levels of a specific protein in the brain improve nerve cell communication in Alzheimer’s?

Majid Mohajerani, Ph.D.
The University of Lethbridge
Lethbridge, Canada

Background

Nerve cells in the brain communicate with each other by releasing and sensing signaling molecules called neurotransmitters. Neurotransmitters physically interact with and bind to docking sites called “receptors” on the surface of nerve cells and activate pathways in these cells. One neurotransmitter, called GABA, is critical for proper nerve cell communication. The activity of GABA becomes  impaired in Alzheimer’s. However, the precise mechanism of how GABA becomes impaired is unknown. Dr. Majid Mohajerani and colleagues believe a specific receptor, called KCC2, which is decreased is Alzheimer’s, may be involved in this process.

Research Plan

Dr, Mohajerani and team will use genetically engineered Alzheimer’s-like mice to examine the role of KCC2 and GABA signaling in Alzheimer’s progression. They will measure both the amount of and location of KCC2 within the brains of these mice. Next, the researchers will correlate the amount and location of KCC2 with changes in overall nerve cell signaling, GABA activity, and cognitive function. Lastly, the team will study whether increasing the amount of KCC2 in the brain prevents cognitive decline in genetically engineered Alzheimer’s-like mice.

Impact

The results of this project may contribute to our understanding of the role of GABA signaling in the progression of Alzheimer’s and may help identify the mechanisms by which GABA signaling becomes impaired. If successful, the results can also inform the development of novel therapeutics for Alzheimer’s.