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.

项目总结（生物标本/神经病理学）： 认知超级老人是80岁以上的人，他们的情景记忆表现至少和 对五六十岁的人来说是正常的考虑到正常情况下与年龄有关的记忆丧失 SuperAgers为研究促进抗性的生物因素提供了独特的资源 以及对年龄对认知的退化影响的恢复力。西北大学的超级老龄化项目 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， 解剖学、病理学和分子特征已在超级老年人中得到鉴定，这些特征将它们与 他们的同龄人与平均认知（控制），包括更大的体积前扣带皮层（ACC），更大的 前扣带皮层中Von Economo神经元的密度， 与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， MAP 2K 3基因的不同多态性。拟议的联盟的目标是增加主题 超级老年人和控制池，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标本/神经病理学核心将收集和储存脑组织， 从参与者的血液制品，提供神经病理学诊断，定量的关键标志物， 神经变性，并生成基因组，转录组和血浆生物标志物数据，用于协作 校内和校外的研究。它还将提供脑组织，血浆和DNA的研究建议， 该联合体的项目2。它将能够在更大的队列中确认以前的发现，并将允许 探索区分超级老年人和对照组的新因素。生物标本/神经病理学核心 我们有三个具体目标：目标1。所有参与者的库存血液/血液制品和DNA，以及 尸检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呈现，DNA的外显子组范围分析的数据， 将生成皮质组织的转录组分析和血浆生物标志物并存档。目标二。确认 以前的生物学，解剖学，病理学和遗传学发现，在一个显着更大的队列的超级老年人和 通过该联盟获得的控制。关于超级衰老表型的现有观察结果， 在小的队列中产生，将在更大的参与者库中得到证实。目标3。探索新的因素， 可以在一个大的队列中区分SuperAgers和Control，包括神经元和突触的测量。 完整调查人员组成的小组具有广泛的专业知识和生产力记录， 实现这一核心目标。生物标本/神经病理学核心的活动将促进 调查可能导致超级衰老表型的因素，并将有助于确定潜在的目标 让正常老年人保持认知功能和对抗痴呆症的干预措施。