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（生物样本/神经病理学）： 认知超级老年人是指 80 岁以上的老年人，其情景记忆表现至少与普通老年人一样好。 对于50-60岁的人来说，这被认为是正常的。鉴于通常发生的与年龄相关的记忆丧失 能力，超级老年人为研究促进抵抗的生物因素提供了独特的资源 以及对年龄对认知的内卷影响的恢复力。西北大学超级老龄化计划已取得 在解决这个问题方面取得了重大进展。在研究过程中，一些生物、 超级老年人的解剖学、病理学和分子特征已被确定，这些特征将他们与 他们的同龄人具有平均认知能力（对照组），包括更大的前扣带皮层（ACC）体积、更大的 前扣带皮层 Von Economo 神经元的密度，较少的皮质斑块和缠结 年龄相关的阿尔茨海默病病理学特征、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。拟议联盟的目标是增加主题 超级老年人和控制池，并实现非裔美国参与者的更高代表性。 超级老化联盟的生物样本/神经病理学核心将收集和储存脑组织 参与者的血液制品，进行神经病理学诊断，定量关键标记物 神经退行性疾病，并生成基因组、转录组和血浆生物标志物数据以进行协作 校内和校外研究。它还将为拟议的研究提供脑组织、血浆和 DNA。 该联合体的项目2。它将能够在更大的队列中确认先前的发现，并将允许 探索区分超级老年人和对照组的新因素。生物样本/神经病理学核心 将追求三个具体目标： 目标 1. 储存所有参与者的血液/血液制品和 DNA，以及 来自参加尸检的参与者的死后脑组织。血液制品以及固定和冷冻的大脑 组织将被储存，神经病理学诊断将被提供，并且数据将来自全外显子组 DNA 分析， 将生成并存档皮质组织和血浆生物标志物的转录组分析。目标2.确认 先前在一个更大的超级老年人群中进行的生物学、解剖学、病理学和遗传学发现 通过该联盟获得的控制权。关于超级老化表型的现有观察结果是 在小规模群体中产生的，将在更大的参与者群体中得到确认。目标 3. 探索新的因素 可以在一大群人中区分超级老年人和对照组，包括神经元和突触的测量 正直。组成的调查人员团队拥有丰富的专业知识和与相关领域相关的生产力记录 实现这一核心目标。生物样本/神经病理学核心的活动将促进 研究可能导致超级衰老表型的因素，并有助于确定潜在目标 旨在帮助正常老年人保持认知功能并对抗痴呆症的干预措施。