MPO CSF/Serum Levels as a Biomarker for Early Alzheimer's Disease

MPO CSF/血清水平作为早期阿尔茨海默病的生物标志物

基本信息

批准号：
8046375
负责人：
WANDA F REYNOLDS
金额：
$ 18.78万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8046375
关键词：
APP gene Alu Elements Alzheimer&apos s Disease Appearance Astrocytes Autopsy Binding Sites Biological Markers Bone Marrow Boston Brain Cerebrospinal Fluid Chloride Ion Chlorides Chronic Cognitive deficits Collaborations Control Groups Dementia Deposition Development Diagnosis Disease Progression Elements Enzymes Event Gadolinium DTPA General Hospitals Genes Goals Health Human Hydrogen Peroxide Hypochlorous Acid Image Impaired cognition Individual Inflammatory Life Longitudinal Studies Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Massachusetts Methods Modeling Monitor Mus Myelogenous Neurons Nitrites Nuclear Receptors Oxidants Parents Pathogenesis Pathology Patients Peroxidases Phospholipids Primates Proteins Protons Reaction Reactive Nitrogen Species Reporting Research Institute SP1 gene Sampling Senile Plaques Serotonin Serum Site Staging Symptoms Techniques Testing The Sun Therapeutic Therapeutic Agents Time Transgenes Transgenic Mice Universities Variant Vascular Dementia Weight aging brain case control chemokine cytokine disorder control follow-up human subject mild neurocognitive impairment mouse model neuron loss normal aging novel novel therapeutics oxidation peroxidation promoter public health relevance sensor small molecule tau Proteins therapeutic evaluation transcription factor

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to determine if myeloperoxidase (MPO) levels or MPO-generated oxidants in cerebral spinal fluid (CSF) or serum provide an early biomarker for Alzheimer's disease (AD). MPO is an oxidant-generating enzyme which is absent from normal aged brain yet abundant in amyloid plaques in AD brain. Our studies have shown that the human MPO gene is aberrantly expressed in astrocytes in AD brain as well as in our huMPO-APP mouse model. Moreover, in the mouse model, MPO expression occurs at early stages prior to significant plaque deposition. Here we propose to investigate whether huMPO levels in CSF or serum constitute a biomarker for early pathology in the humanized MPO-APP23 mouse model. In collaboration with John Chen we will also investigate whether the presence of MPO activity in the brains of these mice can be imaged using a novel MRI technique. We plan to follow-up our mouse studies with the examination of CSF from AD cases and controls. In collaboration with Boston University AD Center and Sun Health Research Institute, we will examine the levels of MPO and its oxidants in CSF from patients with early to late AD and controls. The findings will reveal if MPO or its oxidant byproducts in CSF or serum provide a biomarker to identify patients at an early stage, prior to appearance of symptoms by which time irreversible damage would have occurred. Such biomarkers would also be valuable as a means to monitor the efficacy of novel therapeutic agents and assess disease progression. PUBLIC HEALTH RELEVANCE: It is important to find biomarkers which allow us to diagnose Alzheimer's disease at early stages, prior to appearance of symptoms at which time irreversible damage has already occurred. CSF or serum MPO or MPO-oxidants may represent an accessible biomarker which would help to differentiate between early AD, vascular dementia, and mild cognitive impairment, and assess disease progression. A more reliable biomarker would also be valuable for monitoring the efficacy of novel therapeutics in human subjects as well as mouse models for AD.

描述（由申请人提供）：该项目的目的是确定脑脊髓液（CSF）或血清中的髓过氧化物酶（MPO）水平或MPO生成的氧化剂是否为阿尔茨海默氏病（AD）提供早期的生物标志物。 MPO是一种生成氧化剂的酶，正常脑中不存在AD大脑中淀粉样蛋白斑块中丰富的酶。我们的研究表明，人类MPO基因在AD大脑的星形胶质细胞以及我们的Humpo-App小鼠模型中异常表达。此外，在小鼠模型中，MPO表达发生在显着斑块沉积之前的早期阶段。在这里，我们建议研究CSF或血清中的Humpo水平是否构成人源化MPO-APP23小鼠模型中早期病理的生物标志物。与约翰·陈（John Chen）合作，我们还将研究这些小鼠大脑中MPO活性是否可以使用新颖的MRI技术进行成像。我们计划通过检查AD病例和对照组的CSF来跟进我们的小鼠研究。与波士顿大学广告中心和太阳健康研究所合作，我们将研究早期至晚期和对照的患者CSF中MPO及其氧化剂的水平。这些发现将揭示CSF或血清中的MPO或其氧化剂副产品是否为早期阶段识别患者提供生物标志物，然后在症状出现之前会发生不可逆的损害。这样的生物标志物也将是监测新型治疗剂和评估疾病进展的功效的一种手段。公共卫生相关性：重要的是要找到生物标志物，使我们能够在早期诊断出阿尔茨海默氏病，在出现症状之前，已经发生了不可逆转的损害。 CSF或血清MPO或MPO氧化剂可能代表可访问的生物标志物，这将有助于区分早期AD，血管性痴呆和轻度认知障碍并评估疾病进展。更可靠的生物标志物也将对于监测新型治疗剂在人类受试者中的功效以及AD的小鼠模型的功效。