Discovery of antibody biomarkers for Alzheimer’s Disease

阿尔茨海默病抗体生物标志物的发现

• 批准号: 9265411
• 负责人: Thomas J. Kodadek
• 金额: $ 19.2万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9265411
• 关键词: Adaptive Immune System; Affinity; Alzheimer disease detection; Alzheimer' s Disease; Antibodies; Antibody Binding Sites; Antigens; Binding; Binding Sites; Biological Assay; Biological Markers; Biology; Blood; Blood Tests; Dementia; Development; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic Specificity; Disease; Epitopes; Generations; Goals; Immobilization; Individual; Investigation; Laboratories; Lead; Libraries; Ligands; Light; Medical; Methods; Molecular Conformation; Neurodegenerative Disorders; Pathology; Patients; Sampling; Serum; Source; System; Testing; Validation; Work; antigen binding; biomarker discovery; clinically relevant; combinatorial; diagnostic assay; experimental study; follow-up; hydrophilicity; novel; public health relevance; screening; specific biomarkers

 DESCRIPTION (provided by applicant): The discovery of serum biomarkers for Alzheimer's disease (AD) represents an enormous unmet medical need. This project will further explore the hypothesis that the adaptive immune system might react to unusual antigens produced as a result of AD pathology and as a result produce high levels of antibodies that would not be found in a normal individual. There is some evidence that this is the case. To discover these antibodies we plan to screen large libraries of bead-displayed synthetic oligomers and find compounds that retain far more antibodies from AD serum samples than from controls. These molecules would be employed as first generation "capture agents" for the AD-specific antibodies in a multiplexed Luminex-like diagnostic assay. If this R21 preliminary investigation is successful, it would set the stage for compound optimization and a much larger validation trial that could lead to an effective blood test for AD.

 描述（由申请人提供）：阿尔茨海默病（AD）血清生物标志物的发现代表了巨大的未满足的医疗需求。该项目将进一步探讨适应性免疫系统可能对AD病理学产生的不寻常抗原产生反应的假设，并因此产生在正常个体中不会发现的高水平抗体。有一些证据表明情况确实如此。为了发现这些抗体，我们计划筛选大的珠子展示的合成寡聚体文库，并找到从AD血清样品中保留比对照多得多的抗体的化合物。这些分子将在多重Luminex样诊断测定中用作AD特异性抗体的第一代“捕获剂”。如果这项R21初步研究成功，它将为化合物优化和更大规模的验证试验奠定基础，这可能导致有效的AD血液检测。

项目成果

Asymmetric synthesis of vinylogous β-amino acids and their incorporation into mixed backbone oligomers.

• DOI: 10.1039/c7ob00333a
• 发表时间: 2017-04-11
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Wu H;An H;Mo SC;Kodadek T
• 通讯作者: Kodadek T

Cell-Permeable Peptides Containing Cycloalanine Residues.

• DOI: 10.1002/anie.201605745
• 发表时间: 2016-10-04
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Wu, Hao;Mousseau, Guillaume;Mediouni, Sonia;Valente, Susana T.;Kodadek, Thomas
• 通讯作者: Kodadek, Thomas