Synapses are specialized structures that are critical for the transmission of information between neurons in the brain. Fine-tuning of the electrochemical activity at synapses underlies cognitive processes. In Alzheimer’s disease, memory loss coincides with synapse deterioration. The Tracy lab is investigating the molecular events that lead to synapse dysfunction and cognitive decline in Alzheimer’s disease and frontotemporal dementia. We think that synapses are particularly vulnerable to toxicity early in the progression of dementia before neurons begin to die. Tau, a microtubule-associated protein, accumulates in the brain and becomes toxic to neurons in Alzheimer’s disease and frontotemporal
dementia. We are exploring how tau-mediated toxicity contributes to the emergence of synapse pathophysiology in these diseases. We are using mouse models and human induced pluripotent stem cell (iPSC)–derived neurons to dissect the mechanisms that trigger synapse and neuronal dysfunction during pathogenesis. Our long-term goal is to establish a foundation for new treatment strategies to restore synapse function and cognition at the early stages of disease progression before neurons are lost.