Science

Excitatory neuron expressing human tau (red), AMPA receptor GluA2 (green), and the cell is filled by Azurite (blue).

Our research focuses on understanding the molecular basis for Alzheimer’s disease and other age-related dementias. These investigations combine insights from human brain tissue donated by patients with age-related neurodegenerative diseases, studies in cell culture models, and molecular techniques to uncover new pathways involved in Alzheimer’s disease and other neurodegenerative diseases.

Tau has been implicated in regulating neuronal network activity in the brain and the removal of tau makes mice resistant to seizure activity. Our lab uses cell culture models to uncover the novel roles of tau in neuronal biology, with a focus on the interaction between tau and neuronal activity.

Tau commonly aggregates in the aging human brain, with high levels of tau aggregates associated with memory impairment in older adults. This condition has recently been termed Primary Age-Related Tauopathy (PART). Tau aggregated in PART show a similar morphology and distribution as tau aggregates in Alzheimer’s disease. Our lab uses human tissue from PART and Alzheimer’s disease brain to investigate how tau can cause memory impairment in humans.

Primary age-related tauopathy shown by hematoxylin and eosin staining (left), silver staining (middle), and immunostaining for phosphorylated tau (right).
Silver stain showing amyloid plaques and neurofibrillary tangles (aggregated tau) in Alzheimer’s disease.

Alzheimer’s disease pathology is characterized by the accumulation of extracellular amyloid plaques and intracellular tau aggregates called neurofibrillary tangles. In patients with Alzheimer’s disease, the progression of tau pathology correlates with cognitive decline, implying that tau aggregation may contribute to cognitive decline in Alzheimer’s disease. Our lab combines cell culture models of Alzheimer’s disease and brain tissue from Alzheimer’s disease patients with biochemical and imaging techniques to uncover molecular pathways contributing to tau pathology, with the ultimate goal of finding new potential therapeutic targets for Alzheimer’s disease patients.