Taher Darreh-Shori

Acetylcholine is a molecule important for proper nerve cell communication. This molecule is transported between nerve cells in key areas of the brain where it helps with memory and attention. Nerve cells contain a protein called ChAT (choline-acetyltransferase) that is responsible for producing acetylycholine. In people with Alzheimer’s disease ChAT levels become reduced in brain regions affected by the disease. Changes in ChAT could therefore serve as an early biomarker of Alzheimer’s disease, but currently there is a lack of imaging techniques that can accurately “trace” ChAT levels in the living brain. Research Plan Taher Darreh-Shori, Ph.D. and colleagues have been working to develop novel compounds that can “highlight” ChAT on positron emission tomography (PET) brain scans. PET scans can be used to visualize changes over time in the levels or distribution patterns of certain molecules in the brains of people with Alzheimer’s disease. For their current studies, the researchers will further develop their PET “tracers” for ChAT. They will use research animals to determine how effectively the ChAT tracer can enter the brain when injected into the bloodstream. The researchers also plan to begin testing the safety and dosing of the ChAT tracer in a small human clinical study. Impact If successful, the results of this effort could lead to a novel PET tracer for ChAT that could improve the ability to detect Alzheimer’s disease at the earliest stages. The test could complement the other imaging modalities helping to understand the disease and improve clinical diagnosis. The study may also support the development of disease-modifying treatments by providing a new way to monitor the effectiveness of a drug.