Photocleavage Technology for Blood-based Multi-Biomarker Alzheimer's Disease Assay
用于基于血液的多生物标志物阿尔茨海默病检测的光裂解技术
基本信息
- 批准号:10227129
- 负责人:
- 金额:$ 125万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:Abeta synthesisAffectAffinityAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease diagnosticAlzheimer&aposs disease modelAlzheimer&aposs disease patientAlzheimer’s disease biomarkerAmyloid beta-42Amyloid beta-ProteinAntibodiesArea Under CurveAutomationBehaviorBenchmarkingBiological AssayBiological MarkersBloodBostonBusinessesCalibrationCerebrospinal Fluid ProteinsChronicClinicalCognitiveCross ReactionsCustomDementiaDetectionDeteriorationDevelopmentDiagnosticDisease ProgressionEarly DiagnosisEarly InterventionEvaluationGoldHealth Care CostsImmunoassayImmunodiagnosticsIndustryLeadershipLicensingLiquid substanceLongevityMagnetismMalignant neoplasm of prostateManufacturer NameMeasurementMeasuresMethodsMicrospheresModelingNeurodegenerative DisordersPersonsPharmacologic SubstancePhasePhenotypePopulationPopulation GroupPositron-Emission TomographyPublic HealthROC CurveReaderReportingResearchResearch PersonnelRoboticsRoleSamplingSeminalSenile PlaquesSepharoseSerologySerumServicesSpecificitySpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSpinal PunctureSyndromeTechnologyTherapeuticUniversitiesWorkaptamerbaseclinically relevantcognitive functioncommercializationcostdesigndetection limitdisorder controlhuman old age (65+)improvedmalignant breast neoplasmmultiplex assaymultiplex detectionnovelnovel strategiesparticleprotein biomarkersscreeningtau Proteins
项目摘要
Summary/Abstract
Alzheimer's Disease (AD) is a chronic neurodegenerative disease characterized by progressively worsening
dementia, a syndrome associated with deterioration in cognitive function, behavior and ability to perform everyday
activities. AD currently affects over 5.7 million persons in the U.S. with over 70% over the age of 65 and
approximately 30 million world-wide. The public health costs due to AD is expected to grow exponentially due to
the large expansion of the population over 65 which is estimated to reach over 100 million by 2060. Importantly,
early diagnosis of AD is critical for application of therapeutics early in the disease progression, offering the promise
of reducing debilitating effects and extending life span.
Although the major clinical methods of diagnosing AD rely either on detection of biomarkers such as β-amyloid and
tau proteins from cerebrospinal fluid (CSF) or PET imaging, these assays are limited by their invasiveness (e.g. lumbar
puncture) or high costs, respectively, and not suitable as a front-line AD diagnostic. In contrast, a blood-based assay
would be highly suitable for screening large population groups (e.g. persons over 60) for early AD. While blood-based
assays of single biomarkers show significant promise for early detection of AD (e.g. for β-amyloid), it is likely that a
panel of several biomarkers measured using a multiplex assay will ultimately emerge as necessary to achieve
sufficient specificity to have clinical utility, especially in distinguishing different neurodegenerative diseases that
have similar phenotypes. An additional major problem in the development of sensitive and accurate blood-based
AD assays is the matrix effect. This effect is caused by the presence of the much more abundant molecules in blood
which interfere with detection of the low-abundance biomarkers.
We evaluated and successfully demonstrated during Phase I a new approach to multiplex serological AD assays
termed PC-PURE™ which is designed to both enrich low-abundance biomarkers and eliminate the matrix effect.
This technology is based on the use of novel photocleavable (PC) linkers developed by AmberGen which are
incorporated into affinity capture agents such as aptamers or antibodies. We successfully demonstrated the
feasibility of PC-PURE™ AD immunoassays by enrichment and multiplex detection of 3 model AD biomarkers
(Aβ40, Aβ42 and tau). Our results show that PC-PURE™ when applied as a “front-end” to a commercially available
multiplexed Luminex® xMAP® assay improves sensitivity by 30 to 667-fold compared to the same assay without
PC-PURE™. Furthermore, PC-PURE™ provides a much more accurate estimate of absolute biomarker
concentration since both the calibration curves and biomarkers extracted from the biospecimen are measured in a
similar medium. During Phase II, PC-PURE™ will be further optimized for measurement of a model panel of 16
AD biomarkers using 300 AD confirmed and control serum samples and compared to results obtained using a bead-
based immuno-MALDI-MS method that is currently one of the most accurate means of measuring AD biomarkers
in serum. Commercial products will include PC-PURE™ multiplex immunoassay kits targeting AD biomarkers.
总结/摘要
阿尔茨海默病(Alzheimer's Disease,AD)是一种慢性神经退行性疾病,
痴呆症,一种与认知功能、行为和日常行为能力恶化相关的综合征
活动AD目前影响美国超过570万人,其中超过70%的人年龄在65岁以上,
全世界大约有三千万人。由于AD的公共卫生成本预计将呈指数级增长,
65岁以上的人口大量增加,估计到2060年将超过1亿。重要的是,
AD的早期诊断对于在疾病进展早期应用治疗至关重要,
减少衰弱的影响和延长寿命。
尽管诊断AD的主要临床方法依赖于生物标志物如β-淀粉样蛋白和β-淀粉样蛋白的检测,
由于这些测定法可用于从脑脊液(CSF)或PET成像中检测tau蛋白,这些测定法受到其侵入性(例如腰椎损伤)的限制。
穿刺)或高成本,并且不适合作为一线AD诊断。相比之下,基于血液的检测
将非常适合筛查大人群(例如60岁以上的人)的早期AD。虽然基于血液
单一生物标志物的测定显示出早期检测AD(例如β-淀粉样蛋白)的显著前景,
使用多重测定法测量的一组几种生物标志物将最终成为实现
具有临床实用性的足够特异性,特别是在区分
有相似的表型在开发灵敏和准确的基于血液的
AD测定是基质效应。这种效应是由血液中存在的大量分子引起的
其干扰低丰度生物标志物的检测。
我们在第一阶段评估并成功证明了一种新的多重血清学AD检测方法
被称为PC-PURE™,其被设计为富集低丰度生物标志物并消除基质效应。
该技术基于使用AmberGen开发的新型光可裂解(PC)接头,
结合到亲和捕获剂如适体或抗体中。我们成功地证明了
通过富集和多重检测3种模型AD生物标志物的PC-PURE™ AD免疫测定的可行性
(Aβ40、Aβ42和tau)。我们的研究结果表明,PC-PURE™作为“前端”应用于市售
多重Luminex® xMAP®测定法与不使用的相同测定法相比,灵敏度提高了30至667倍。
PC-PURE™。此外,PC-PURE™提供了绝对生物标志物的更准确的估计。
因为从生物样本提取的校准曲线和生物标志物两者都是在生物样本中测量的,
类似的介质。在第二阶段,PC-PURE™将进一步优化,用于测量16个模型面板
使用300份AD确认血清和对照血清样品的AD生物标志物,并与使用珠粒获得的结果进行比较。
基于免疫MALDI-MS的方法,是目前测量AD生物标志物的最准确方法之一
在血清中。商业产品将包括靶向AD生物标志物的PC-PURE™多重免疫测定试剂盒。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mark Lim其他文献
Mark Lim的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mark Lim', 18)}}的其他基金
New Technology for High-Resolution Antibody Profiling for SARS-CoV-2
SARS-CoV-2 高分辨率抗体分析新技术
- 批准号:
10481680 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
A Highly Multiplexed, Multiomic 3D Mouse Brain Map Using MALDI-IHC
使用 MALDI-IHC 绘制高度多重、多组学 3D 小鼠脑图
- 批准号:
10603396 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
Photocleavable Mass-Tags for Spatial Multiomics of Alzheimer’s Brain Tissue
用于阿尔茨海默病脑组织空间多组学的光裂解质量标签
- 批准号:
10684250 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
A Highly Multiplexed, Multiomic 3D Mouse Brain Map Using MALDI-IHC
使用 MALDI-IHC 绘制高度多重、多组学 3D 小鼠脑图
- 批准号:
10705203 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
New Technology for High-Resolution Antibody Profiling for SARS-CoV-2
SARS-CoV-2 高分辨率抗体分析新技术
- 批准号:
10686794 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
Photocleavable Mass-Tags for Spatial Multiomics of Alzheimer’s Brain Tissue
用于阿尔茨海默病脑组织空间多组学的光裂解质量标签
- 批准号:
10483988 - 财政年份:2022
- 资助金额:
$ 125万 - 项目类别:
Highly Multiplexed Nanoscale Mass Spectrometric Imaging of Cancer Tissues
癌症组织的高度多重纳米级质谱成像
- 批准号:
9908822 - 财政年份:2018
- 资助金额:
$ 125万 - 项目类别:
Highly Multiplexed Nanoscale Mass Spectrometric Imaging of Cancer Tissues
癌症组织的高度多重纳米级质谱成像
- 批准号:
10019483 - 财政年份:2018
- 资助金额:
$ 125万 - 项目类别:
Photocleavage Technology for Improved Serum-based Multi-Biomarker Cancer Assays
用于改进基于血清的多生物标志物癌症检测的光裂解技术
- 批准号:
9175644 - 财政年份:2016
- 资助金额:
$ 125万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 125万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 125万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 125万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 125万 - 项目类别:
Grant-in-Aid for Early-Career Scientists