A Diagnostic Platform for Extracellular Vesicle-Derived Biomarkers - Towards Early Detection of Alzheimer's Disease

细胞外囊泡衍生生物标志物的诊断平台 - 迈向阿尔茨海默病的早期检测

• 批准号: 10629620
• 负责人: Kristen Dellinger
• 金额: $ 14.07万
• 依托单位: NORTH CAROLINA AGRI & TECH ST UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629620
• 关键词: Address; Affect; Affinity; Alzheimer disease detection; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease care; Alzheimer' s disease diagnosis; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid beta-42; Amyloid beta-Protein; Area; Binding; Biological; Biological Assay; Biological Markers; Biomedical Research; Biosensing Techniques; Biosensor; Blood; Blood specimen; Caring; Cerebrospinal Fluid; Characteristics; Clinical; Clinical assessments; Cognitive; Cognitive Therapy; Complex; Coupled; Dementia; Detection; Development; Devices; Diagnosis; Disease; Early Diagnosis; Early Intervention; Effectiveness of Interventions; Endowment; Engineering; Environment; Enzyme-Linked Immunosorbent Assay; Executive Dysfunction; Exhibits; Experimental Designs; Foundations; Goals; Gold; Human; Impaired cognition; Individual; Institutionalization; Language; Long-Term Care; Molecular; Monitor; Neurofibrillary Tangles; Neurons; North Carolina; Optics; Participant; Patients; Pharmacologic Substance; Positioning Attribute; Protein Isoforms; Proteins; Raman Spectrum Analysis; Rapid screening; Recording of previous events; Research; Research Support; Sampling; Screening procedure; Senile Plaques; Sensitivity and Specificity; Serum; Societies; Source; Specificity; Spectrum Analysis; Spinal Puncture; Surface; Symptoms; Technology; Time; Treatment outcome; Underrepresented Populations; United States National Institutes of Health; Universities; Update; Visuospatial; Western Blotting; Work; biochip; care costs; clinical diagnostics; clinical practice; cost effective; design; detection limit; diagnostic criteria; diagnostic platform; diagnostic screening; early detection biomarkers; economic cost; effective intervention; extracellular vesicles; graduate student; improved; induced pluripotent stem cell; multidisciplinary; novel; patient prognosis; point of care; pre-clinical; predictive marker; prognostic tool; rational design; routine practice; routine screening; screening; societal costs; tau Proteins; tau-1; tool; undergraduate student

A Diagnostic Platform for Extracellular Vesicle-Derived Biomarkers: Towards Early Detection of Alzheimer’s Disease PROJECT SUMMARY. Alzheimer’s disease (AD) poses a growing burden on our society, with cases expected to reach 12.7 million by 2050. While research supports biomarkers for early detection, most Alzheimer’s patients are diagnosed after exhibiting clinical symptoms. At this stage, the advanced progression of senile plaques and neurofibrillary tangles pose significant challenges to effective interventions. Moreover, established biomarkers, such as amyloid beta-42/amyloid beta-40 and phosphorylated tau, are currently limited to analysis in cerebrospinal fluid, making their potential for routine screening nearly impossible. Thus, there is a critical need for novel, non-invasive approaches to rapidly screen for preclinical Alzheimer’s to facilitate the application of early interventions, such as physical, pharmaceutical, and cognitive therapies. Recent work has demonstrated the potential of circulating extracellular vesicles as a promising source of biomarkers to monitor and diagnose various diseases, including AD. However, accessible technologies to accurately detect AD-associated extracellular vesicles and their constituents are not currently in clinical practice. Moreover, concentrations in blood are present in the low pico- to femtomolar range, limiting conventional detection by ELISA and Western blot. This proposal aims to address these critical needs and focuses on developing a new platform to detect tau in neuron-derived extracellular vesicles (NDEVs). We hypothesize that ultrasensitive detection (< 5 pg/mL) of NDEV-tau can be achieved by optimizing our surface-enhanced Raman spectroscopy (SERS) nanotag technology using a rational design-of-experiment approach. If our hypothesis is correct, we expect this work to serve as the foundation for developing a point-of-care device that can be used for routine screening of pre-symptomatic AD. With this goal in mind, we will focus on the following specific aims: (1) Synthesize ‘SERS nanotags’ with a high affinity for NDEV-tau and identify the characteristics for effective binding; (2) Assess NDEV-tau sensitivity and specificity using the SERS platform in spiked human serum. Ultimately, we expect to establish the limit of detection and sample volumes needed for accurate tau detection. By engineering SERS-active substrates for ultrasensitive detection of NDEV-tau, we can then build upon this platform to enhance the multiplexing of several AD-associated biomarkers in complex biological samples. Our long-term goal is to develop SERS-based bioanalysis to drastically improve current standards in molecular detection for AD in both clinical and research settings.

细胞外囊泡衍生生物标志物的诊断平台