Cytotoxic Fragment of Amyloid Precursor Protein Accumulates in Hippocampus after Global Forebrain Ischemia

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Abstract
We developed an antibody specific to β-amyloid precursor protein (βAPP) fragments possessing the exact amino terminus of the β-amyloid peptide and examined its induction in postischemic hippocampus. In control hippocampus, this APP fragment was lightly observed in pyramidal neurons of CA sectors and dentate granule cells. Transient forebrain ischemia enhanced accumulation of the APP fragment in CA1 pyramidal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA3 neurons, it disappeared in dead CA1 neurons. While astrocytes did not show in any immunoreactivity throughout the experiment, those in the CA1 sector showed moderate immunoreactivity 7 days after the ischemia. The APP fragment has a cytotoxic effect on cultured neurons. These results suggest that the accumulation of the cytotoxic APP fragment in CA1 neurons may play a role in the development of delayed neuronal death after the ischemic insult.