Improved immunoprofiling to diagnose Alzheimer's Disease

描述(申请人提供)：阿尔茨海默病(AD)是美国老年人最常见和最衰弱的神经退行性疾病之一。有几种治疗方法在减缓阿尔茨海默病的发展方面显示出了希望，但为了真正有效，它们必须在阿尔茨海默病完全出现之前就开始治疗。阿尔茨海默病的盛行期会产生轻度认知障碍(MCI)的症状，但理想的测试应该在MCI出现之前就发现早期AD的迹象。最近的一些数据支持炎症过程对AD的发展很重要的观点。 我们实施了一项名为多光子检测(MPD)的新技术，支持一系列高 敏感度诊断测试。在这一应用中，MPD用于针对细胞因子的分析，并应用于导致AD的炎症过程。目前的检测方法不够灵敏，无法可靠地检测血清中的细胞因子。我们将证明，建议的方案是足够敏感和实用的，可以用于轻度认知障碍(MCI)和AD的血液筛查。拟议研究的具体目标是： 目的1：进一步提高检测肿瘤坏死因子-α、干扰素-γ、白介素1-β和白介素6的灵敏度 目的2：建立亚pg/mlIL-18检测方法 目的3：优化超灵敏、基于脑脊液的细胞因子检测方法 目的：通过对MCI/AD患者和健康对照血清的检测，验证该方法的有效性。

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 prodominate 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. Some recent data supports the view that inflammatory processes are important to the development of AD. We implemented a new technique, called Multiphoton Detection (MPD) supporting a family of high sensitivity diagnostic tests. In this application, MPD is used in assays targeting cytokines and applied to inflammatory processes leading to AD. The current assays are not sensitive enough to reliably measure cytokines in serum. We will demonstrate that the proposed protocols are sensitive and practical enough to be used as blood based screening assays for mild cognitive impairment (MCI) and AD. The specific aims of the proposed studies are: Aim 1: Further improvement of sensitivity of immunoassays for TNF-alpha, IFN-gamma, IL-1 beta and IL-6 Aim 2: Development of sub-pg/ml assay for IL-18 Aim 3: Optimization of ultrasensitive, CSF based assays of cytokines Aim 4: Validation of this assay by testing serum from MCI/AD patients and healthy controls.