Measuring blood markers to diagnose Alzheimer's Disease

描述（由申请人提供）：阿尔茨海默病（AD）是美国老年人最常见和使人衰弱的神经退行性疾病之一。有几种治疗方法有望减缓阿尔茨海默病的发展，但要真正有效，就必须在阿尔茨海默病全面发作之前开始。阿尔茨海默病的前驱期会产生轻度认知障碍（MCI）的症状，但理想的测试可以在MCI出现之前就发现早期阿尔茨海默病的迹象。该项目的目标是开发一种测试方法，可以通过测量血液中与阿尔茨海默病相关的大脑蛋白质的水平来检测其变化。由于血液中tau和bAP等蛋白质的含量非常低，因此需要进行非常敏感的测试。BioTraces已经开发了两种具有必要灵敏度的免疫测定方法IA/MPD和Super-ELISA。然而，尽管这些检测可以测量血液中的tau和bAP，但血液中的总水平可能反映了血脑屏障的完整性，就像大脑的绝对水平一样。因此，还提出了一种测量血液中磷酸化tau蛋白与总tau蛋白比率的测试方法，因为该比率似乎增加了甚至基于csf的测试的特异性，并且该比率对血脑屏障变化的敏感性应该低得多。在将tau和bAP的检测方法发展到所需的灵敏度之后，将通过测量和比较患有AD或MCI的人和没有AD或MCI的人的血液样本来验证这些检测方法。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is one of the most common and debilitating neurodegenerative diseases of older Americans. Several treatments show promise in slowing the development of AD, but to be truly effective, they must be started before full-blown AD appears. The prodromal phase of AD produces symptoms of mild cognitive impairment (MCI), but an ideal test would detect signs of incipient AD even before the appearance of MCI. The goal of this project is to develop a test that can detect changes in brain proteins that are associated with AD by measuring their levels in blood. Since the levels of these proteins such as tau and bAP are very low in blood, a very sensitive test is needed. BioTraces has developed two immunoassays, IA/MPD and Super-ELISA that have the requisite sensitivity. However, even though these assays can measure tau and bAP in the blood, the total levels in blood might reflect the integrity of the blood-brain barrier as much as the absolute brain levels. Thus, a test to measure the ratio of phosphorylated to total tau in blood is also proposed since this ratio appears to increase the specificity even of CSF-based tests and the ratio should be much less sensitive to variations in the blood-brain barrier. After developing the assays to tau and bAP to the required sensitivity, they will be validated as AD tests by measuring and comparing blood samples from people with and without AD or MCI.