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淀粉样前体蛋白（APP）是一种高度保守的蛋白质， 一种多功能蛋白，在广泛的组织中表达 在哺乳动物的生命周期中。 秘书长的正常职能 人们对蛋白质的了解很少，但来自各种来源的证据表明， 表明参与细胞接触、生长和修复过程， 以及止血。 该蛋白的异常表达及其与 多种修饰形式与阿尔茨海默病（AD）有关。 因此，重点主要是理解 APP mRNA和蛋白产物的转录后修饰， 但对APP及其在发病机制中的作用的全面了解 需要对转录控制的类似理解， APP基因表达，特别是在发育背景下。 在目前的拨款建议中，我们引入了一种新的方法， 快速产生APP基因控制的详细信息， 在完整的生物体经历正常的 个体发育 这将通过首先建立正常 通过原位免疫显微镜观察APP表达模式。 其次，我们将在转基因小鼠中使用APP报告基因构建体， 确定APP基因的亚区的调节作用， 与APP基因表达的正常模式进行比较。 三是 将采用分子方法来检测特定的反应元件， 然后通过转基因方法证实该分析。 我们有 已经确定了这种方法对其他基因的有效性， 我们已经开始将这种分析应用于APP基因，特别是在 中枢神经系统的发展和细胞分化的背景下， 巨核细胞谱系的血液元素。

The Amyloid Precursor Protein (APP) is a highly conserved multifunctional protein, showing expression in a broad range of tissues during the mammalian life cycle. The normal functional role(s) of the protein is poorly understood, but evidence from a variety of sources suggest an involvement in cell contact, growth, and repair processes as well as hemostasis. The abnormal expression of the protein and its multiple modified forms has been implicated in Alzheimer's Disease (AD). Heretofore, emphasis has been directed primarily to an understanding of post-transcriptional modification of the APP mRNA and protein products, but a complete understanding of APP and its role in pathogenesis requires a comparable understanding of the transcriptional control of APP gene expression, particularly within a developmental context. In the present grant proposal, we introduce a new methodology designed to rapidly produce detailed information on the control of APP gene regulation in the context of the intact organism undergoing normal ontogeny. This will be accomplished by first establishing the normal patterns of APP expression by means of in situ immunomicroscopy. Secondly, we will use APP reporter constructs in transgenic mice to determine the regulatory role of subregions of the APP gene in comparison with the normal patterns of APP gene expression. Thirdly, we will employ molecular methods to detect specific response elements, and then confirm this analysis by means of the transgenic approach. We have already established the efficacy of this approach with other genes, and we have begun to apply this analysis to the APP gene specifically in the context of the development of the CNS and the cytodifferentiation of the megakaryocyte lineage of the blood elements.