UAB neurologist Erik Roberson, M.D., Ph.D., uses clinical observations to guide his laboratory research, focusing on the ways that disease interferes with the brain’s ability to store and retrieve memories. In particular, he is interested in cognitive deficits related to Alzheimer’s. Initially, researchers assumed that the memory loss in Alzheimer’s was a result of neuronal death, but Roberson says that the process actually begins earlier.
Most research related to the cause of Alzheimer’s disease has focused on two proteins: amyloid beta and tau. But changes in amyloid beta occur in the pre-symptomatic stages of the disease. By the time patients are diagnosed with Alzheimer’s, the levels of amyloid beta in their brains are so high that drugs to target the protein may not have an effect, Roberson notes. This could explain why clinical trials of such drugs have not been very successful.
Since the changes in tau happen closer to the onset of symptoms, Roberson suggests that it may be a more relevant target for treating patients showing the clinical signs of Alzheimer’s. Supporting this idea, he found that eliminating tau in animal models prevents the cognitive deficits caused by amyloid beta. “We think that tau is modifying what the amyloid beta does,” he says. “There’s something about the presence of tau that is permissive for amyloid beta to exert its adverse effects.”
Since turning off all of the tau in the human brain would be very difficult, Roberson is looking for other ways to block specific functions. His research suggests that another protein, Fyn—also involved in learning and memory—interacts with tau to exert pathologic effects. Roberson’s lab is now collaborating with researchers at Southern Research Institute to find and study drugs that block the interaction between the proteins.