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2018 Alzheimer's Association Research Grant (AARG)

Targeting feed-forward inhibition in DG-CA3 to improve memory in AD

Can restoring balance in the brain cell activity reduce beta-amyloid accumulation and improve memory

Amar Sahay
Massachusetts General Hospital
Boston, MA - United States


Specific types of nerve cells in the brain send signals that could excite or suppress the activity of the brain cell network- respectively known as excitatory and inhibitory nerve cells. Recent studies indicate a loss of balance in these signals in genetically engineered Alzheimer’s-like mouse models and in individuals with Mild Cognitive Impairment – mild loss of memory that often precedes Alzheimer’s.  Other studies have shown that restoring the balance of excitatory and inhibitory nerve cell activity reduces the accumulation of the protein fragment beta-amyloid in the brain—a characteristic of Alzheimer’s—and improves cognition in mice and humans.

Research Plan

Dr. Amar Sahay will use a genetically engineered Alzheimer’s-like mouse model to examine whether there is an imbalance in  the two signals (exciting and suppressing) produced by the nerve cells in the brain. The researchers will then introduce a factor called Ablim3 that has been shown to improve the communication between excitatory and inhibitory nerve cells in the brain. Dr. Sahay will examine whether Ablim3 slows the accumulation of beta-amyloid and improves memory in the genetically-engineered Alzheimer’s-like mice.


Understanding how the imbalance in excitatory and inhibitory nerve cell activity in the brain is associated with the accumulation of beta-amyloid and cognitive decline may reveal new approaches to restoring this balance and slowing the progression of Alzheimer’s.

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