Early Steps in the Processing of Amyloid Precursor Protein

APP is synthesized in a part of the cell called the endoplasmic reticulum (ER), where it undergoes a number of changes. In AD, the processing of APP is altered, leading to overproduction of the amyloid protein Ab42. However, it is not yet clear what causes the production of Ab42 in the ER. Dr. Goldgaber has hypothesized that as APP is synthesized and inserted into the ER, it interacts with specialized proteins called chaperones. Chaperones are known to be important in helping newly synthesized proteins fold into their proper three-dimensional shape. In Dr. Goldgaber’s hypothesis, the interaction between APP and chaperones is required to ensure that the APP is properly modified and processed. He believes that misfolded or mutant APP may be targeted for some type of protein degradation, which could lead to the production of Ab42. He is exploring a number of approaches for studying the role of chaperones in the processing of normal and mutant APP.