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Apoptotic Cell Death Induced by β-Amyloid1–42 Peptide Is Cell Type Dependent
Authors:Martin Gschwind  Gerda Huber
Institution:Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland
Abstract:Abstract: β-Amyloid peptide (Aβ), a proteolytic fragment of the β-amyloid precursor protein, is a major component of senile plaques in the brain of Alzheimer's disease patients. This neuropathological feature is accompanied by increased neuronal cell loss in the brain and there is evidence that Aβ is directly neurotoxic. In the present study reduced cell viability in four different neuroblastoma cell types was observed after treatment with human Aβ1–42 for 1 day. Of the cell types tested rat PC12 and human IMR32 cells were most susceptible to Aβ toxicity. Chromosomal condensation and fragmentation of nuclei were seen in PC12, NB2a, and B104 cells but not in IMR32 cells irrespective of their high sensitivity to Aβ. Electrophoretic analysis of cellular DNA confirmed internucleosomal DNA fragmentation typical for apoptosis in all cell types except IMR32. These findings suggest that the form of Aβ-induced cell death (necrosis or apoptosis) may depend on the cell type.
Keywords:β-Amyloid peptide  Alzheimer's disease  Neurotoxicity  Necrosis  Apoptosis
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