Brain PET Imaging of Synaptic Density in Alzheimer’s Dementia

A new PET tracer may improve Alzheimer’s disease detection and progression

Ming-Kai Chen, M.D., Ph.D.

Yale University, New Haven, CT

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

September 2015, for 3 years

Funding Amount:

$200,000

Lay Summary

A new PET tracer may improve Alzheimer’s disease detection and progression

Can a new PET imaging tracer outperform the currently used one in diagnosing Alzheimer’s disease (AD) and in monitoring its progression?

Diagnosing probable AD currently relies on three major measures. One is whether there is a decrease in glucose metabolism in major cognitive areas in the brain, suggesting lower brain activity. This assessment is made by PET imaging, using a tracer called FDG which measures glucose metabolism. A second measure is the amount of the protein called amyloid that builds up in the brain. Amyloid can be measured by PET using tracers such as PiB which binds to amyloid. The third measure is neurocognitive testing results. But results from the first of these measures, FDG-PET imaging, are confounded by several factors that are prevalent in the elderly population: medication use; high blood glucose levels associated with diabetes; and distractions in the clinical environment.

A new PET imaging tracer, called [C-11]-UCB-J, may be able to eliminate those confounding factors and outperform FDG-PET in helping clinicians diagnose AD and monitor its progression. Instead of measuring glucose like FDG-PET does, this new tracer measures a glycoprotein called SV2A. This protein is found at all brain cell synapses, where one brain cell transmits an electrochemical message to another. The investigators hypothesize that this tracer can quantify the density of brain synapses and therefore identify synaptic loss in AD, and that this measure will be a more reliable indicator of AD diagnosis and its progression compared to FDG-PET.

They will test this hypothesis in three ways. First, they will use their new PET tracer to compare synaptic density in ten AD patients and ten healthy volunteers; they expect to find less binding of the tracer in the AD patients compared to the volunteers, indicating that the patients have synaptic loss. Second, in the same 20 participants, the investigators will determine whether their PET tracer shows a greater magnitude of difference between the AD patients and healthy volunteers compared to that seen on FDG-PET imaging. Third, they will determine whether the severity of each AD patient’s cognitive functioning, as measured by cognitive testing, correlates better with the brain scan findings from their PET tracer compared to those from FDG-PET.

Significance: This study will provide preliminary evidence of whether this new PET imaging tracer, which measures synaptic loss, has the potential to become the new gold standard for diagnosing AD and assessing the disease’s progress.

Investigator Biographies

Ming-Kai Chen, M.D., Ph.D.

Dr. Ming-Kai Chen received his MD from the National Taiwan University Medical College. He completed a research fellowship in nuclear medicine at the Johns Hopkins Hospital. Subsequently, he received his Ph.D. in the molecular imaging program at the Johns Hopkins University. In order to conduct relevant translational and clinical research, he finished clinical nuclear medicine residency training at Yale-New Haven Hospital. He is currently an Assistant Professor in Diagnostic Radiology at Yale University, nuclear medicine physician at Yale-New Haven Hospital, and co-medical director of the Yale PET Center. Dr. Chen has substantial experience and training in molecular imaging and neuroscience in small animals, nonhuman primates, and human subjects. His primary research interests are translational research and molecular neuroimaging in Alzheimer’s disease and multiple sclerosis from bench work to clinical application. In addition, he is also actively involved in the clinical application of molecular imaging in oncology.