随着我国年龄结构老龄化的加剧，老年痴呆(AD)已成为社会日益严峻的健康问题。目前对AD 还没有客观有效的诊断标准，主要依靠患者病史及临床表现，易受主观因素影响，难以进行早期诊断。如何在Aβ斑块沉积早期对AD 进行早期诊断是目前影像学上的难题，且具有现实意义。近年研究证实，Aβ斑块沉积与淀粉蛋白前β位分泌酶1（BACE1）的酶的活性增强与过表达有关，因此如果能据此机制设计出特异性高的分子探针，在分子水平.上检测BACE1 的活性与表达，结合患者临床表现，即可对AD 病人进行早期诊断。本项目拟采用一系列对BACE1 选择性高的小分子化合物进行F-18 正电子标记，并利用标记化合物进行脑内BACE1 显像，期望建立明确的客观诊断标准，实现AD 的早期诊断。此项工作在国内外属首次，对于在分子水平研究AD 进程具有开创性的意义。

As the aging of China's age structure becomes more and more serious in recent years, Alzheimer's disease (AD) has become an increasingly serious health problem. Because there is no effective and objective diagnostic criteria for AD, nowadays diagnosis of AD mainly rely on medical history and clinical manifestation and it is vulnerable to subjective factors, early diagnosis of AD is very difficult. Diagnosis of early stage AD at the beginning of the deposition of β-amyloid plaques is a difficult and meaningful task. Previous research shows that the deposition of β-amyloid plaques associated with the upregulation of beta-site APP cleaving enzyme 1 (BACE1). Early diagnosis of AD becomes possible if we can design and synthesis this kind of molecular probes with high specificity and affinity with BACE1.In this project we plan to synthesis and labeling a series of compounds that has high affinity with BACE1 and these compounds will be tested and evaluated in imaging experiments, such studies will be helpful to find a new way to the early diagnosis of AD.This an original work and will be helpful in basic research of AD at molecular level。