AB and AICD accumulation, does IDE play a role in vivo?

Suzanne Guenette, PhD
Massachusetts General Hospital (Charlestown, MA)
Year Awarded:
2003
Grant Duration:
April 1, 2003 to March 31, 2005
Disease:
Alzheimer's Disease
Award Amount:
$200,000
Grant Reference ID:
A2003041
Award Type:
Standard
Award Region:
US Northeastern

AB and AICD accumulation, does IDE play a role in vivo?

Summary

Details


The goal of this study is to analyze the role of a protein, called the insulin-degrading enzyme (IDE), in the development of Alzheimer's disease (AD). IDE has the ability to break down proteins, including two products of the amyloid precursor protein (APP), the beta-amyloid peptide and the APP intracellular domain (AICD) and an insulin protein that plays an important role in the development of diabetes. IDE is capable of degrading the free form of beta-amyloid, when it is not in its aggregated form. Genetic studies suggest that IDE may be responsible for an increased risk of developing Alzheimer's disease in individuals over the age of 65. However, so far no mutations have been found in the IDE gene. This study will address the impact, if any, of IDE on the development of AD-related pathology in an animal model that has been modified to develop Aß plaques.

Publications

Farris, W., Schutz, S.G., Robak, A., Chang, A.Y., Selkoe, D.J., and Guenette, S.Y. (2005) Modulation of AB levels and associated neuropathology by insulin - degrading enzyme in APP transgenic mice. [conference abstract]

Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E.A., Frosch, M.P., Eckman, C.B., Tanzi, R.E., Selkoe, D.J. and Guenette, S. (2003) Insulin- degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA. 100(7):4162-4167 [Alzforum Recommended Paper]  

Guenette, S.Y. (2003) Mechanisms of Abeta clearance and catabolism.Neuromolecular Medicine. 4(3):147-60.  
 

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