IMPLEMENTATION OF BIOFLUID MARKERS FOR EARLY DETECTION OF ALZHEIMER'S DISEASE AND OTHER NEURODEGENERATIVE DISEASES IN COLOMBIA

在哥伦比亚实施生物流体标记物以早期检测阿尔茨海默病和其他神经退行性疾病

• 批准号: 10537769
• 负责人: Gloria Patricia Cardona-Gómez
• 金额: $ 26.5万
• 依托单位: UNIVERSITY OF ANTIOQUIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10537769
• 关键词: Age; Alzheimer disease detection; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid beta-Protein; Area; Biological; Biological Markers; Blood; Brain; Clinical Research; Collaborations; Collection; Colombia; Colombian; Country; Data; Dementia; Detection; Diagnosis; Disease Progression; Early Diagnosis; Fatty Acids; Future; Genotype; Glial Fibrillary Acidic Protein; Goals; Human; Impaired cognition; Individual; Infrastructure; Institution; International; Kansas; Late Onset Alzheimer Disease; Liquid substance; Mass Spectrum Analysis; Modification; Monitor; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurosciences; Pathogenicity; Patients; Peripheral; Phospholipids; Plasma; Population; Prevention; Reporting; Research; Research Infrastructure; Research Personnel; Resolution; S-nitro-N-acetylpenicillamine; Sampling; Serum; Services; Standardization; Statistical Algorithm; Statistical Data Interpretation; System; Technology; Training; Universities; aged; apolipoprotein E-4; base; biobank; cognitive performance; cohort; detection method; early detection biomarkers; familial Alzheimer disease; genetic variant; improved; lipidomics; member; neurovascular unit; prediction algorithm; presenilin-1; protective allele; research study; tau Proteins

Biomarker fluids are a less expensive option for studying the AD and other neurodegenerative diseases populations. However, we have not available this technology for helping to the early or antemortem diagnosis, and also for the support of new findings and peripheral biomarkers proposals. The main aim of this project is to enhance the future capability of the Neuroscience Group of the University of Antioquia (GNA) to develop new clinical research for the prevention of Alzheimer’s disease. Our Institution has been internationally recognized for its clinical research trajectory. However, in order to take full advantage of our well-characterized human brain GNA´s biobank with the largest collection available worldwide of biological samples with familial Alzheimer’s Disease (AD) and other neurodegenerative conditions. Our research infrastructure remains in need to improve its basic-bench research capabilities. Using these unique samples cohorts, our ultimate goal is to establish the necessary infrastructure to implement the use of biofluid markers for Alzheimer´s disease and other neurodegenerative diseases in Colombia, for future clinical research studies and the early detection, diagnosis, prevention and treatment of AD in the country. Specifically, i) We will establish the infrastructure for the detection of biomarkers in blood (plasma and serum) of individuals with familial Alzheimer´s disease (AD). The Colombian team, led by Drs. Lopera (Co-PI) and Cardona (PI) will transfer SIMOA technology to assemble the necessary infrastructure to standardize the detection and quantification of blood biomarkers such as: Amyloid Beta (AB) 40/AB42, total tau, pTau-181, NfL, GFAP, SNAP-25 from Quanterix. In collaboration with Dr Yakeel Quiroz (co-PI), Steven Arnold (Co-Investigator), investigators from the Colombian team will get training in advanced methods for the detection of blood biomarkers and their association with the progression of neurodegeneration and cognitive decline in Alzheimer’s disease and other dementias. Also, ii a) We will determine early biomarkers in a cohort of familial Alzheimer´s patients carrying highly penetrant mutations and AD-associated gene variants. In order to identify early biomarkers of AD, capable of monitoring disease progression from carriers and non-carriers of PSEN1 mutations, also including different pathogenic PSEN1 mutations, as well as pathogenic and protective variants and members with late-onset AD. Finally, based at the hypothesis that: “Phospholipids (PL) composition at the endomembrane system of the neural cells report early modifications of the neurovascular unit alteration to the periphery”, ii b) We will explore the standardization of new peripheral markers for early prediction of dementia. We will use high resolution mass spectrometry (MS) to validate our preliminary data on the phospholipid profile and fatty acid composition of serum from E280A-Familial AD patients in four different stages (8-12 yo, 13-19 yo, 20-30 yo, 30-40 years old and symptomatic 40 y older, and sporadic patients) and aged-matched asymptomatic carriers and non-carrier controls. These samples will be obtained from the biobank of “Group of Neuroscience de Antioquia” and from strong collaboration with Dr. Area-Gomez´s Lab at Columbia University (Co-Researcher). We will optimize a multivariate statistical analysis and algorithm of prediction to define the association between age, genotype, cognitive performance and phospholipidic profile. All lipidomics studies will be performed in collaboration with the Lipidomic Center of Kansas University between Dr. Welti´s Lab (scientific service) and Dr. Area-Gomez.

生物标记物液体是研究AD和其他疾病的较便宜的选择 神经退行性疾病人群。然而，我们还没有提供这项技术 帮助早期或临终诊断，并支持新的发现 和外围生物标记物的建议。这个项目的主要目标是提升未来 安蒂奥基亚大学(GNA)神经科学小组开发新技术的能力 预防阿尔茨海默病的临床研究。我们的制度一直是 其临床研究轨迹得到国际认可。然而，为了充分利用 我们拥有最大收藏量的人脑GNA S生物库的优势 家族性阿尔茨海默病(AD)和其他疾病的生物样本在全球范围内可用 神经退行性疾病。我们的研究基础设施仍然需要改进其 基础研究能力。使用这些独特的样本队列，我们的最终目标是 建立必要的基础设施，以实施生物流体标志物的使用 哥伦比亚的阿尔茨海默病、S病和其他神经退行性疾病，用于未来临床 阿尔茨海默病的研究和早期发现、诊断、预防和治疗 国家。具体地说，i)我们将建立检测生物标志物的基础设施 家族性阿尔茨海默病S病患者的血液(血浆和血清)。这个 由洛佩拉博士(Co-Pi)和卡多纳(Pi)领导的哥伦比亚团队将把SiMoA 技术来组装必要的基础设施，以使检测和 血液生物标志物的定量，如：淀粉样β(AB)40/AB42，总tau，ptau-181， 来自Quanterix的NFL、GFAP、SNAP-25。与Yakeel Quiroz博士(合伙)合作，Steven Arnold(联合调查员)，哥伦比亚团队的调查人员将接受高级培训 血液生物标志物的检测方法及其与肿瘤进展的关系 阿尔茨海默病和其他痴呆症患者的神经退化和认知能力下降。另外， II a)我们将确定S携带的家族性阿尔茨海默病患者的早期生物标记物 高穿透性突变和AD相关基因变异。为了及早识别 AD的生物标志物，能够监测携带者和非携带者的疾病进展 PSEN1突变，还包括不同的致病PSEN1突变以及 晚发性阿尔茨海默病的致病和保护性变异及其成员。最后，基于 假说：“血管内膜系统的磷脂组成。 神经细胞报告外周神经血管单位改变的早期修改“， II b)我们将探索用于早期预测的新的外周标志物的标准化 痴呆症。我们将使用高分辨率质谱仪(MS)来验证我们初步的 E280A家系血清磷脂组成和脂肪酸组成的研究 4个不同阶段的AD患者(8-12岁、13-19岁、20-30岁、30-40岁和 有症状的40岁以上和散发性患者)和年龄匹配的无症状携带者 和非承运人控制。这些样本将从“Group of”生物库获得。 神经科学De Antioquia》以及与AREA-GOMEZ博士S实验室的密切合作 哥伦比亚大学(合作研究员)。我们将优化多变量统计分析和 定义年龄、基因型、认知能力之间关联的预测算法 性能和磷脂特性。所有的脂质组学研究都将在 韦尔蒂·S博士实验室与堪萨斯大学脂质组学中心的合作 (科学服务)和Area-Gomez博士。