We discovered that abnormal TGF-β signaling may contribute to Alzheimer’s disease using a number of engineered mouse models that allow us to regulate TGF-β signaling in different cell types. Other studies showed that TGF-β1 can promote acute immune responses in the CNS and lead to increased immune cell infiltration after vaccination with CNS peptides. These and other mice which lack TGF-β receptors in neurons or report activation of signaling by producing indicator proteins are currently being used to study the role of TGF-β signaling in normal CNS function and disease. To try to exploit the beneficial effects of TGF-β signaling in neurons we are developing small molecule activators of this pathway.

TGF-β type II receptors (green) are expressed by neurons in the brain of mice (NeuN [neuronal marker], red)