Enhanced BK-induced calcium responsiveness in PC12 cells expressing the C100 fragment of the amyloid precursor protein

Several lines of evidence have implicated the amyloid precursor protein (AP P) and its metabolic products as key players in Alzheimer's disease (AD) pa thophysiology. The approximately 100 amino acid C-terminal fragment (C100) of APP has been shown to accumulate intracellularly in neurons expressing f amilial AD (FAD) mutants of APP and to cause neurodegeneration when express ed in transfected neuronal cells. Transgenic animals expressing this fragme nt in the brain also exhibit some neuropathological and behavioral AD-like deficits. Here, we present evidence that PC12 cells expressing the C100 fra gment either via stable transfections or herpes simplex virus-mediated infe ctions show alterations in calcium handling that are similar to those previ ously shown in fibroblasts from AD patients. This alteration in calcium hom eostasis may contribute to the deleterious effects of C100 in PC12 cells. O ur data also lend support for a pathophysiological role for C100 since it i nduces an alteration thought to play an important role in AD pathology. (C) 1999 Elsevier Science B.V. All rights reserved.