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2006 Grant - Vassar
The Role of Intraneuronal Abeta in Alzheimer's Disease Pathophysiology
Robert J. Vassar, Ph.D.
Feinberg School of Medicine
2006 Investigator-Initiated Research Grant
The primary component of amyloid plaques, a hallmark of Alzheimer's disease pathology, is the beta-amyloid protein fragment. Amyloid plaques reside in the spaces between brain cells, but beta-amyloid appears to first accumulate inside neurons. Beta-amyloid's toxic effect on neurons may, therefore, happen internally before amyloid plaques form outside cells.
Robert J. Vassar, Ph.D., and colleagues have developed genetically altered mice that carry a human Alzheimer-related gene mutation. These mice may serve as an effective model for studying early deposits of beta-amyloid inside neurons. The mice start to accumulate beta-amyloid in neurons at about six weeks of age. They do not develop amyloid plaques until two months of age. Furthermore, the death of neurons appears to be the event that enables the formation of plaques outside of cells.
In this current study, the investigators will more carefully characterize the accumulation of beta-amyloid in mouse neurons. They hope to determine where beta-amyloid accumulates in cells, what kind of beta-amyloid structures form inside the cell, and how cell degeneration and death relates to internal accumulation of beta-amyloid. They will also examine the potential role of a protein that may mediate the accumulation and toxicity of beta-amyloid inside neurons. This work may clarify key steps in disease processes and provide important data for drug development efforts.