CYTOTOXIC FRAGMENT OF AMYLOID PRECURSOR PROTEIN ACCUMULATES IN HIPPOCAMPUS AFTER GLOBAL FOREBRAIN ISCHEMIA

We developed an antibody specific to beta-amyloid precursor protein (b eta APP) fragments possessing the exact amino terminus of the beta-amy loid peptide and examined its induction in postischemic hippocampus. I n control hippocampus, this APP fragment was lightly observed in pyram idal neurons of CA sectors and dentate granule cells. Transient forebr ain ischemia enhanced accumulation of the APP fragment in CA(1) pyrami dal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA(3) neurons, it disappe ared in dead CA(1) neurons. While astrocytes did not show in any immun oreactivity throughout the experiment, those in the CA(1) sector showe d moderate immunoreactivity 7 days after the ischemia. The APP fragmen t has a cytotoxic effect on cultured neurons. These results suggest th at the accumulation of the cytotoxic APP fragment in CA(1) neurons may play a role in the development of delayed neuronal death after the is chemic insult.