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One of the primary focuses this year for Mr. Kulstad was on developing a tissue-culture model of
Amyloid-Beta (Aß) degradation in a hepatocellular carcinoma-derived (Hep-G2) cell line. These cells
have been shown to internalize and degrade the protein, and Mr. Kulstad has an assay that
quantitatively measures degradation using radio-labeled Aß. Mr. Kulstad has been able to show that
changes in the concentration of insulin, as well as other specific inhibitors of insulin degrading
enzyme (IDE) can reduce Aß degradation in this model. This has led us to hypothesize that IDE
mediates this degradative process, and we are further characterizing this model in an effort
understand the role of the liver and IDE in the peripheral clearance of Aß. It is thought that a
reduction in Aß clearance in the periphery could affect deposition in the brain, a process central
to the development of Alzheimer’s disease. This work was presented at the Society for Neuroscience
meeting in Dec. 2003, program # 944.22.
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