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Document Type

Feature Article

Publication Date

Fall 9-1-2007

Publication Title

Washington University Undergraduate Research Digest: WUURD 3(1)


Peer Editor: Ramana Gorrepati; Faculty Mentor: Gunnar Gouras

Amyloid-beta (Aβ) is a peptide largely responsible for the amyloid plaques that form in the brains of Alzheimer’s disease patients. An increase in the concentration of a specific type of Aβ, Aβ42, has been linked to familial and sporadic Alzheimer’s disease. An understanding of where Aβ42 is generated will give much needed insight into the process involved in amyloid plaque formation. Because Aβ42 is a small peptide located in the middle of the APP gene, distinguishing Aβ42 from its larger counterpart, APP, has proven especially difficult. Common tags such as green fluorescent protein (GFP) cannot be used due to the inability of Aβ to accommo- date them. To address this, a construct was generated using a tetra- cysteine tag inserted into a region deigned potentially redundant for Aβ function given the normal generation of Aβ 1-40/42 and Aβ 11- 40/42. Using both live cell imaging and fluorescent microscopy, the movement of Aβ throughout a cell can be tracked and knowledge as to where Aβ is generated and transported in a neuron relative to APP can be known. In order to better understand the process of Aβ generation, an alter- native method was developed. Using a Y- secretase inhibitor and sub- cellular markers, buildup of C-terminal fragments of APP can be observed and the location of Aβ formation can be deduced.

From the Washington University Undergraduate Research Digest: WUURD, Volume 3, Issue 1, Fall 2007. Published by the Office of Undergraduate Research.

Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Co-editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor.


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