2024 Alzheimer's Association Research Grant (AARG)

Preclinical evaluation of potential cholinergic PET imaging tracers

Can PET imaging tracers detect early brain changes associated with Alzheimer’s disease?

Taher Darreh-Shori, Ph.D.
Karolinska Institutet
Stockholm, Sweden

Background

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 acetylcholine. 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 monitor or “trace” ChAT levels in the living brain.

In earlier research, Dr. Taher Darreh-Shori and colleagues identified 10 “tracer” molecules 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.

Research Plan

Dr. Darreh-Shori and colleagues will further develop their PET “tracers” for ChAT and test them using genetically engineered Alzheimer's-like and genetically engineered ALS-like animal models and human tissue from individuals with Alzheimer’s and ALS. They will use genetically engineered ALS-like rats to determine how effectively the ChAT tracers can detect a decrease in ChAT compared to healthy rats. The researchers also plan to begin testing the safety and dosing of ChAT tracers in non-human primates.

Impact

If successful, the results of this effort could lead to a novel PET tracer that may improve the ability to detect Alzheimer’s disease at the earliest stages. The test could complement other imaging modalities that help to understand the disease and improve clinical diagnosis.