LeBlanc A C, Xue R, Gambetti P
Department of Neurology and Neurosurgery, McGill University, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada.
J Neurochem. 1996 Jun;66(6):2300-10. doi: 10.1046/j.1471-4159.1996.66062300.x.
Amyloid precursor protein (APP) gives rise by proteolytic processing to the amyloid beta peptide (A beta) 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 A beta, 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 A beta than astrocytes or microglia.
淀粉样前体蛋白（APP）经蛋白水解加工产生淀粉样β肽（Aβ），在阿尔茨海默病患者脑内的老年斑中大量存在。APP在脑中高度表达。为评估脑内Aβ的来源，通过脉冲/追踪标记以及对APP和APP代谢片段进行免疫沉淀，研究了新生大鼠大脑皮层主要细胞类型中APP的代谢情况。我们描述了一种新的C末端截短的APP异构体，它似乎仅在神经元中产生。通过磷光成像对神经元、星形胶质细胞和小胶质细胞中APP的合成、降解及代谢进行了定量分析。结果显示，虽然在这三种培养物中，通过淀粉样生成途径代谢的APP很少，但神经元产生的Aβ似乎比星形胶质细胞或小胶质细胞更多。
