Measuring blood markers to diagnose Alzheimer's Disease

测量血液标记物以诊断阿尔茨海默病

• 批准号: 6833336
• 负责人: Andrzej K Drukier
• 金额: $ 10万
• 依托单位: BIOTRACES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833336
• 关键词: Alzheimer' s disease; amyloid proteins; biomarker; biotechnology; blood brain barrier; blood tests; clinical research; diagnosis design /evaluation; diagnostic tests; early diagnosis; geriatrics; human tissue; immunologic assay /test; patient oriented research; phosphorylation; posttranslational modifications; tau proteins

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.

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最令人衰弱的神经退行性疾病之一。几种治疗方法在减缓AD的发展方面显示出希望，但要真正有效，它们必须在全面的AD出现之前开始。AD的前驱期产生轻度认知障碍（MCI）的症状，但理想的测试将在MCI出现之前检测到早期AD的迹象。该项目的目标是开发一种测试，可以通过测量血液中与AD相关的脑蛋白的水平来检测其变化。由于这些蛋白质如tau和bAP在血液中的水平非常低，因此需要非常敏感的测试。BioTraces已经开发了两种具有必要灵敏度的免疫测定法，IA/MPD和Super-ELISA。然而，即使这些测定可以测量血液中的tau和bAP，血液中的总水平可能与绝对脑水平一样反映血脑屏障的完整性。因此，还提出了测量血液中磷酸化tau与总tau的比率的测试，因为该比率似乎甚至增加了基于CSF的测试的特异性，并且该比率对血脑屏障的变化应该不太敏感。在将tau和bAP检测开发到所需的灵敏度后，将通过测量和比较患有和不患有AD或MCI的人的血液样本来验证它们作为AD检测。