We study the behavioral and molecular basis of memory losing using transgenic mouse models, with specific interest in Alzheimer’s disease and frontotemporal dementia. We recently found that, prior to synapse loss, phosphorylated tau mislocalizes to the dendritic spines and impairs cognition. Current efforts include elucidating the pathway by which tau mislocalizes and identifying the downstream changes, both molecular and behavioral, that result from tau mislocalization. Techniques used in the lab include neuropharmacology, operant conditioning, transgenic animals, isolation and characterization of the postsynaptic density (PSD), and measures of protein expression using western blot analysis. By focusing on early synaptic changes, we hope to identify novel strategies for the prevention of Alzheimer’s disease, rather than treating the symptoms of synapse loss that occur in later stages of the disease. 

Current studies include (1) identifying behavioral tasks sensitive to the earliest deficits in these mice, (2) identifying how risk factors for Alzheimer's disease, such as aging and metabolic disorders, may modulate early synaptic changes and using these changes to identify and pilot early methods of prevention, (3) determining the role of extracellular glutamate in tau pathology, and (4) determining whether treatments aimed at reducing extracellular glutamate rescue tau pathology and memory deficits.

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