2023 Alzheimer's Association Research Grant (AARG)

A BCAA-Lowering Compound as a Novel Approach to Delay the Onset of AD

Could a new therapeutic compound delay the onset of dementia by targeting multiple Alzheimer’s-associated brain changes?

Andrew Shin, Ph.D.
Texas Tech University
Lubbock, TX - United States

Background

Branched-chain amino acids (BCAAs) are essential amino acids that are not produced in our bodies, so they must be obtained from the foods we eat. However, studies suggest that too many BCAAs in the blood may lead to harmful brain changes. These include reducing neurotransmitters, chemicals that nerve cells use to send signals to neighboring nerve cells. Studies have also linked excess BCAAs to nerve cell dysfunction and death and a toxic process called excitotoxicity, in which brain cells become overexcited. These BCAA-associated brain changes are also characteristic of Alzheimer’s. 

Dr. Andrew Shin and colleagues believe that lowering circulating BCAAs may work to delay the onset of Alzheimer’s. In initial studies, genetically engineered Alzheimer’s-like mice fed a BCAA-restricted diet showed fewer biological and cognitive changes associated with Alzheimer’s.

Research Plan

Since limiting BCAA intake from dietary sources could be challenging for many individuals, Dr. Shin and colleagues will study the effectiveness of a BCAA-lowering compound called BT2. The researchers will investigate the optimal dose of BT2 that results in reduced Alzheimer’s-related brain changes in genetically engineered Alzheimer’s-like mice. They will also study whether administering BT2 improves nerve cell functioning and delays cognitive decline in these mice. 

Impact

If successful, the findings may support BT2 as a novel therapeutic agent that prevents the onset of Alzheimer’s by impacting multiple targets in the brain.