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Research Grants - 2005


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Research Grants 2005


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2005 Grant - Golde

Novel Animal Models of Amyloid Deposition

Todd Eliot Golde, M.D., Ph.D.
Mayo Clinic
Jacksonville, Florida

2005 Zenith Fellows Award

A leading hypothesis of Alzheimer's disease proposes that accumulation of the beta-amyloid protein fragment in the brain triggers a series of pathological events that disrupt cell-to-cell communication, destroy cells and cause dementia. While a great deal of evidence supports this hypothesis, there are gaps in our understanding of beta-amyloid's function.

Some of these gaps are the limitations of current disease models, usually genetically engineered mice that carry at least one human Alzheimer-related gene and produce an excess of beta-amyloid. Although these models have revealed much about the disease, they invariably have limitations. In particular, the brains of these mice usually don't experience the degree of cell loss seen in Alzheimer's disease or exhibit the same concentration of certain pathological features.

Todd Eliot Golde, M.D., Ph.D., and colleagues are testing a new strategy to develop an animal model that may more closely resembles Alzheimer's disease processes in the human brain. The researchers will test the utility of a novel mechanism to deliver individual beta-amyloid protein fragments to mouse and guinea pig brains. They will then determine whether these models develop a brain pathology that closely resembles Alzheimer's. The researchers will examine variant forms of this approach to determine how best to model certain aspects of Alzheimer's disease changes in the brain. Improvements in animal models may benefit a number of investigations of disease processes and treatment strategies.