Proteomics of mild cognitive impairment in the elderly

老年人轻度认知障碍的蛋白质组学

• 批准号: 7106523
• 负责人: Scott E Counts
• 金额: $ 18.43万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7106523
• 关键词: Alzheimer' s disease; biomarker; biotechnology; cerebrospinal fluid; clinical research; cognition disorders; early diagnosis; entorhinal cortex; human tissue; liquid chromatography mass spectrometry; pathologic process; proteomics; surface enhanced laser desorption ionization; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): Dementia research has become increasingly focused on the prodromal stages of Alzheimer's disease (AD). Elucidating the mechanisms of disease pathogenesis and the reliable identification of people in early stages of cognitive decline will be critical to the development of efficacious therapies for AD. Recently, a clinical entity termed mild cognitive impairment (MCI) has been recognized as a transitional state between the cognitive changes seen in normal aging and AD. The prevalence of MCI is more than double that of dementia and in many cases MCI may be prodromal AD. Therefore, MCI is a suitable condition for exploring the neurobiology underlying AD pathogenesis. There is a paucity of data on pathological and biological markers that distinguish individuals with MCI from healthy aged individuals. To investigate pathobiological markers for MCI, we will employ a novel two-tiered, discovery-based proteomics approach. First, we will use two-dimensional gel electrophoresis (2DGE) and liquid chromatography-tandem mass spectrometry (LCMS/ MS) to identify specific alterations in protein levels in the entorhinal cortex (EC) of subjects with no cognitive impairment (NCI), MCI, or early stage/mild AD. The EC is the initial site of degeneration in MCI and is an ideal area to explore MCI pathogenesis. Second, we will use new surface-enhanced laser desorption/ionization-time of flight MS (SELDI-TOF MS) protein chip technology to evaluate the changes in the cerebrospinal fluid (CSF) of these same individuals. Both tissue and fluid samples will be obtained from our ongoing NIA-funded longitudinal study of aging and AD, the Religious Orders Study (ROS). The proposed studies will hopefully lead to the discovery of new proteins involved in the pathogenesis of AD and new biomarkers for the timely diagnosis of persons in the earliest stages of this devastating disease. Both of these factors will be critical for the development of neuroprotective strategies for slowing or preventing cognitive decline in the elderly.

描述（由申请人提供）：痴呆症的研究越来越集中在阿尔茨海默病（AD）的前驱阶段。阐明疾病的发病机制和早期认知衰退患者的可靠识别对于开发有效的AD治疗方法至关重要。最近，一种被称为轻度认知障碍（MCI）的临床实体被认为是正常衰老和AD认知变化之间的过渡状态。MCI的患病率是痴呆症的两倍多，在许多情况下，MCI可能是前驱AD。因此，MCI是探索AD发病机制的神经生物学基础的合适条件。目前缺乏区分轻度认知障碍患者与健康老年人的病理和生物学标志物的数据。为了研究MCI的病理生物学标志物，我们将采用一种新的两层、基于发现的蛋白质组学方法。首先，我们将使用二维凝胶电泳（2DGE）和液相色谱-串联质谱（LCMS/ MS）来识别无认知障碍（NCI）、MCI或早期/轻度AD受试者的内嗅皮质（EC）中蛋白质水平的特定变化。EC是MCI退行性变的起始部位，是探索MCI发病机制的理想区域。其次，我们将使用新的表面增强激光解吸/电离飞行时间质谱（SELDI-TOF MS）蛋白芯片技术来评估这些个体的脑脊液（CSF）的变化。组织和液体样本将从我们正在进行的nia资助的衰老和AD的纵向研究——宗教秩序研究（ROS）中获得。所提出的研究将有望导致发现与阿尔茨海默病发病机制有关的新蛋白质和新的生物标志物，以便在这种毁灭性疾病的早期阶段及时诊断患者。这两个因素对于减缓或预防老年人认知能力下降的神经保护策略的发展至关重要。