Welcome to the Town Lab!
The Terrence Town Lab at the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC in Los Angeles focuses on developing an immune-based approach to treating Alzheimer’s disease (AD). Most therapies used to target the disease are thwarted by the blood-brain barrier, a natural mechanism that protects brain cells from intrusion, and by the fact that immune responses in the brain are typically muted. But, in our studies, in which laboratory mice have been programmed to develop Alzheimer’s-like disease, we found that certain immune cells could be coaxed from the periphery into the brain, where they attacked the damaging sticky plaque buildup that is a defining feature of Alzheimer’s disease.
We are continuing to pursue this line of research in hopes of developing a next-generation drug to treat Alzheimer’s disease. In parallel, we are extremely interested in better understanding basic Alzheimer’s disease etiology. This work, which has been funded by the National Institutes of Health, the Alzheimer’s Association, and the American Federation for Aging Research, has been published in numerous peer-reviewed journals. Specifically, our work has led to more than 100 research papers, some of which have been published in Science, Nature, Nature Neuroscience, Immunity, and PNAS.
Just last year, we generated the first rat model of AD that manifests all of the clinic-pathological hallmarks of the human syndrome. We made transgenic rats that over-express two mutant human transgenes that are each independently causative of familial early-onset AD: “Swedish” mutant APP and deltaE9 mutant PS1. Unlike their transgenic mouse cousins that develop brain amyloid deposits but fail to manifest the other two defining features of AD, tauopathy and frank neuronal loss, these transgenic rats-for the first time-develop the full spectrum of AD pathologies. Nearly 50 outside laboratories have requested this exciting new tool, and we have just sent these animals to Nobel laureate Stanley Prusiner’s laboratory in collaboration with his group to study prion disease in these animals.