Biospecimen/Neuropathology Core

生物样本/神经病理学核心

• 批准号: 10276530
• 负责人: CHANGIZ GEULA
• 金额: $ 56.31万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10276530
• 关键词: Address; African American; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Anatomy; Anterior; Archives; Autopsy; Biological; Biological Factors; Biological Markers; Blood; Blood Banks; Blood Cells; Brain; Characteristics; Cognition; Cognitive; Collection; DNA; DNA analysis; Data; Dementia; Diagnosis; Elderly; Episodic memory; Extramural Activities; Freezing; Funding; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Intervention; Investigation; Light; MAP2K3 gene; Measures; Memory Loss; Molecular; Nerve Degeneration; Neurofibrillary Tangles; Neurons; Participant; Pathologic; Pathology; Pathway interactions; Performance; Phenotype; Plasma; Productivity; Research Personnel; Resistance; Resources; Synapses; Tissues; Universities; Variant; age effect; age related; blood product; brain tissue; cholinergic; cingulate cortex; cognitive function; cohort; combat; comorbidity; density; exome; inflammatory marker; nerve supply; neurofilament; neuropathology; novel; peer; preservation; programs; protein TDP-43; resilience; transcriptome; transcriptomics; white matter

PROJECT SUMMARY (Biospecimen / Neuropathology): Cognitive SuperAgers are 80+ year-olds with episodic memory performance that is at least as good as what would be considered normal for 50-60-year-olds. Given the normally occurring age-related loss of memory capacity, SuperAgers provide a unique resource for investigating the biological factors that promote resistance and resilience to the involutional effects of age on cognition. The Northwestern SuperAging Program has made considerable progress in addressing this question. In the course of investigations, a number of biologic, anatomic, pathologic, and molecular features have been identified in SuperAgers, which distinguish them from their peers with average cognition (Controls), including greater volume of anterior cingulate cortex (ACC), greater density of Von Economo neurons in the anterior cingulate cortex, fewer cortical plaques and tangles that are characteristic of age-related Alzheimer pathology, integrity of cortical cholinergic innervation and inheritance of different polymorphisms of the MAP2K3 gene. The goal of the proposed Consortium is to increase the subject pool of SuperAgers and Controls and to achieve a much higher representation of African American participants. The Biospecimen / Neuropathology Core of the SuperAging Consortium will collect and bank brain tissue and blood products from participants, render neuropathological diagnoses, quantitate key markers of neurodegeneration, and generate genomic, transcriptomic and plasma biomarker data for collaborative intramural and extramural studies. It will also provide brain tissue, plasma and DNA for studies proposed in Project 2 of this Consortium. It will enable the confirmation of previous findings in a larger cohort, and will allow exploration of new factors that distinguish SuperAgers from Controls. The Biospecimen / Neuropathology Core will pursue three specific aims: Aim 1. Bank blood / blood products and DNA from all participants, and postmortem brain tissue from participants that come to autopsy. Blood products, and fixed and frozen brain tissue will be banked, neuropathological diagnoses will be rendered and data from exome-wide analysis of DNA, transcriptome analysis of cortical tissue, and plasma biomarkers will be generated and archived. Aim 2. Confirm previous biologic, anatomic, pathologic and genetic findings in a significantly larger cohort of SuperAgers and Controls obtained through this Consortium. Existing observations on the SuperAging phenotype, which were generated in small cohorts, will be confirmed in a larger pool of participants. Aim 3. Explore new factors that may distinguish SuperAgers from Controls in a large cohort, including measures of neuronal and synaptic integrity. The assembled team of investigators has extensive expertise and record of productivity relevant to achieving the goals of this core. The activities of the Biospecimen / Neuropathology Core will facilitate investigation of factors that may contribute to the SuperAging phenotype and will help identify potential targets for interventions that will allow normal elderly to preserve cognitive function and combat dementia.

项目摘要(生物医学/神经病理学)： 认知超老者是80岁以上的人，他们的情节记忆表现至少和什么一样好 对于50-60岁的人来说是正常的。鉴于正常发生的与年龄相关的记忆力丧失 能力，超级老人为研究促进抗性的生物因素提供了独特的资源 以及对年龄对认知进化影响的适应能力。西北大学的超级老龄化计划已经做出了 在解决这一问题方面取得了相当大的进展。在调查过程中，一些生物， 超老患者的解剖学、病理学和分子特征已被确认，这是他们与 认知水平一般的同龄人(对照组)，包括前扣带回(ACC)体积较大的同龄人， Von Economo神经元在前扣带回皮质的密度，皮质斑块和缠结较少 老年性阿尔茨海默病的病理特点、皮质胆碱能神经支配的完整性和遗传性 MAP2K3基因的不同多态性。提议的联合体的目标是增加主题 超级老年人和控制者的集合，并实现非洲裔美国人参与者的更高代表性。 超级老龄化联盟的生物医学/神经病理学核心将收集和储存脑组织和 来自参与者的血液产品，提供神经病理诊断，量化关键标志物 神经退化，并为协作生成基因组、转录和血浆生物标记物数据 校内和校外研究。它还将提供脑组织、血浆和DNA，用于在 这个联合体的项目2。它将使以前的发现能够在更大的队列中得到确认，并将允许 探索区分超级老人和控制者的新因素。生物有机磷农药/神经病理学核心 将追求三个具体目标：目标1.保存所有参与者的血液/血液产品和DNA，以及 身体解剖的参与者的死后脑组织。血液制品，固定和冰冻的脑 组织将被储存，神经病理诊断将被提交，来自外显子组范围的DNA分析的数据， 皮质组织的转录组分析和血浆生物标记物将被生成并存档。目标2.确认 先前的生物学，解剖学，病理学和遗传学发现在一个显著更大的超级老年和 通过该联盟获得的控制权。现有的关于超老表型的观察结果是 在小群体中产生的，将在更大的参与者池中得到确认。目标3.探索新的因素 可能在一个大的队列中区分超级老年组和对照组，包括神经元和突触的测量 正直。组建的调查团队拥有广泛的专业知识和与以下方面相关的生产力记录 实现这个核心的目标。生物学家/神经病理学核心的活动将促进 调查可能导致超老表型的因素，有助于确定潜在的靶标 用于干预措施，使正常老年人保持认知功能并与痴呆症作斗争。