HEAT-SHOCK INDUCES ABNORMALITIES IN THE CELLULAR-DISTRIBUTION OF AMYLOID PRECURSOR PROTEIN (APP) AND APP FUSION PROTEINS

The heat shock or stress response may play a role in the pathogenesis of Alzheimer's disease. We conducted experiments to visualize microsco pically the distribution of wild type amyloid precursor protein (APP) and the behavior of an APP deletion mutant under stress. This was achi eved by heat-shock treatment of cells expressing fusion recombinant AP P proteins ragged with secreted placental alkaline phosphatase (SEAP). The fusion proteins were cleaved and secreted in a manner similar to wild type APP in unstressed control cells. SEAP activity was detected by cytochemical methods within the cytoplasm in less than 10% of trans fected unstressed cells. Heat shocked cells showed a striking differen ce from the control cells in that over 90% of the stressed cells displ ayed strong intracytoplasmic SEAP activity occurring with Golgi-like p attern and/or membranous distribution. The effects of heat shock were not due to a peculiar behavior of the clones and depended on the APP p ortion of the constructs. This study shows miscompartmentalization of APP under stress. Such cellular changes may bear important implication s in the processing of APP.