Deconstructing the Dopamine/Abnormal Tau Relationship in Alzheimer’s Disease

Brian Kraemer, PhD
VA Puget Sound Health Care System (VAPSHCS) (Seattle, WA)
Year Awarded:
2014
Grant Duration:
July 1, 2014 to June 30, 2018
Disease:
Alzheimer's Disease
Award Amount:
$250,000
Grant Reference ID:
A2014438S
Award Type:
Standard
Award Region:
US Northwestern

This grant is made possible in part by a bequest from the John A. Beaty Trust.

Brian Kraemer, PhD

Dopamine Signaling Controls Pathological Tau

Summary

A number of neurodegenerative disorders feature tau deposits, including Alzheimer’s disease. These abnormal aggregations of tau protein can cause age-dependent neurodegeneration. We have identified a class of drugs that prevent abnormal tau formation in animal models of Alzheimer’s disease. The goal of this project is to understand how these experimental drugs prevent abnormal tau so that we can develop these drugs further, ultimately setting the stage for clinical trials in Alzheimer’s patients.

About the Researcher

The mission of my research program is to understand the molecular mechanisms at work in age- related cognitive decline caused by neurodegeneration. The relationship between neurodegenerative changes and protein aggregation are of particular interest. Investigations in my laboratory utilize both genetic and chemical biology approaches to explore the means by which abnormal tau protein contributes to neurotoxicity. Our general strategy is to use simple C. elegans models of tauopathy as the primary discovery platform and then validate findings using mammalian cell culture, transgenic mouse models, and study of postmortem human tissue exhibiting pathological tau. Our combined experience dealing with transgenic C. elegans models, human cultured cell models, and transgenic mouse models of tauopathy make us uniquely qualified to conduct these translational experiments.
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