Amyloid Precursor Protein Metabolism in Primary Cell Cultures of Neurons, Astrocytes, and Microglia |
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Authors: | Andréa C LeBlanc Run Xue Pierluigi Gambetti |
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Institution: | Department of Neurology and Neurosurgery, McGill University, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada;and; Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, U.S.A. |
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Abstract: | Abstract: Amyloid precursor protein (APP) gives rise by proteolytic processing to the amyloid β peptide (Aβ) found abundantly in cerebral senile plaques of individuals with Alzheimer's disease. APP is highly expressed in the brain. To assess the source of cerebral Aβ, the metabolism of APP was investigated in the major cell types of the newborn rat cerebral cortex by pulse/chase labeling and immunoprecipitation of the APP and APP metabolic fragments. We describe a novel C-terminally truncated APP isoform that appears to be made only in neurons. The synthesis, degradation, and metabolism of APP were quantified by phosphorimaging in neurons, astrocytes, and microglia. The results show that although little APP is metabolized through the amyloidogenic pathways in each of the three cultures, neurons appear to generate more Aβ than astrocytes or microglia. |
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Keywords: | Amyloid precursor protein Amyloid β peptide Amyloid precursor protein metabolism Neurons Astrocytes Microglia |
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