Betty Tuller, Ph.D.

Glucose Hypometabolism and Amyloid Plaque Formation in AD: A Dual-Tracer PET Study

One roadblock to our understanding of AD has been the scarcity of diagnostic tools that can be used effectively in living humans. Although our understanding of the biochemistry of AD has improved greatly over the past decade, this improvement has come largely from animal models. These animal models are specifically designed to isolate one aspect of a complex, multidimensional disease. When humans are studied, the most common methods used are behavioral evaluation and/or neuroimaging. The latter has generally involved functional MRI to focus on the cognitive deficits associated with AD, and MRI or PET to highlight the structural or metabolic deterioration that can be observed even during rest. Intriguingly, the metabolic deterioration shown with PET occurs specifically in brain areas associated with memory processes.

In the present proposal, we take an interdisciplinary approach to the study of AD progression in humans. To this end, we combine neuroimaging with neuropsychological evaluation of memory processes. We will use a novel dual-tracer paradigm in which both glucose metabolism and p-amyloid plaque accumulation are measured via FDG and PIB, respectively. While FDG is a radioactively-labeled tracer that has long been used in PET research to measure glucose utilization by the brain, PIB has been used as a tracer since January 2004. By using both compounds in the same scanning session, we can observe whether the change in brain metabolism indexed by glucose utilization is accompanied by a buildup of p-amyloid plaque and whether one or both of these processes correlates with the cognitive decline over time. Moreover, glucose utilization in the brain will be observed not during a rest state but just after the subject has been engaged in a series of memory tasks devised specifically to uncover the type of memory deficits common in AD.