Exploring the link between the muscle proteome, physical activity, cognitive resilience and Alzheimer's disease

探索肌肉蛋白质组、体力活动、认知弹性和阿尔茨海默病之间的联系

• 批准号: 10285732
• 负责人: Joshua N. Adkins
• 金额: $ 49.06万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-08 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285732
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; American; Autopsy; Brain; Brain Pathology; Cessation of life; Clinical Trials; Cognition; Cognitive; Data; Dementia; Development; Elderly; Freezing; Health; Impaired cognition; Individual; Intervention; Knowledge; Link; Medical History; Memory; Molecular; Monitor; Motor; Muscle; Muscle Development; Muscle Proteins; Outcome; Participant; Pathologic; Pathology; Patient Self-Report; Phenotype; Physical Exercise; Physical activity; Protein Analysis; Proteins; Proteome; Proteomics; Sampling; Testing; Wrist; active lifestyle; aging population; brain health; cognitive benefits; cognitive function; drug development; drug discovery; effective therapy; exercise intervention; human old age (65+); improved; indexing; link protein; novel; prevent; protein biomarkers; quadriceps muscle; resilience

PROJECT SUMMARY No effective treatments are available to reduce the consequences of pathologic Alzheimer's disease (AD) and related pathologies on cognitive decline and AD dementia in our aging population. While the link between physical activity and cognition is well-documented, the molecular mechanisms underlying its cognitive benefit have not yet been identified. This knowledge gap is a barrier for physical activity interventions to prevent AD and related dementias (ADRD) and cognitive decline in old age. This proposed supplement will apply the large-scale muscle proteomics platform developed by MoTrPAC project to muscle samples from deceased well-characterized older participants of the Memory and Aging Project at Rush Alzheimer's Disease Center to discover muscle proteins impacted by physical activity in older adults and identify proteins which may link a higher level of physical activity with better cognition and reduced odds of dementia prior to death. The proposed project will leverage available data and biospecimens from Memory and Aging Project including annual cognitive and motor testing, self-report medical history and physical activity. Quantitative physical activity metrics are extracted from multiday recordings from a wrist-worn monitor during everyday living. Brain indices of ADRD pathologies are collected from decedents undergoing autopsy and frozen quadriceps muscle is available. The project has two objectives: 1) Quantify the proteome in postmortem quadriceps muscle samples (N = 500) from well-characterized older adults. Apply the large-scale muscle proteomics platform developed by MoTrPAC project for relative quantification of ~8,000 proteins in quadriceps muscle samples. 2) Identify muscle proteins which link a higher level of physical activity with better cognition and reduced odds of dementia in older adults. A multistage analysis will be used to identify muscle proteins related to a) physical activity and b) cognition proximate to death. Then analyzing proteins related to both phenotypes, we will identify proteins that link physical activity with better cognition.

项目摘要 没有有效的治疗方法可以减少阿尔茨海默氏病（AD）和 我们老龄化人群认知能力下降和AD痴呆的相关病理。而 体育锻炼和认知有据可查，其认知益处的分子机制 尚未确定。这种知识差距是防止AD的体育锻炼干预措施的障碍 和相关的痴呆症（ADRD）和老年认知下降。 该提出的补充剂将应用Motrpac开发的大规模肌肉蛋白质组学平台 项目从已故良好特征的老年参与者的记忆和衰老中的肌肉样本项目 在阿尔茨海默氏病中心的项目中，发现肌肉蛋白受到年龄较大的体育锻炼影响的肌肉蛋白 成人并确定可能将较高水平的体育活动与更好的认知联系起来的蛋白质 死亡前痴呆症的几率。 拟议的项目将利用内存和老化项目的可用数据和生物测量，包括 年度认知和运动测试，自我报告病史和体育活动。定量物理 活动指标是从日常生活中从腕上磨损监视器的多日录音中提取的。脑 ADRD病理的索引是从尸检和冰冻股四头肌肌肉的死者那里收集的 可用。该项目有两个目标： 1）量化较旧的年龄较大的左右股四头肌样品（n = 500）中的蛋白质组 成年人。应用Motrpac项目开发的大型肌肉蛋白质组学平台 在股四头肌样品中定量约8,000种蛋白质。 2）确定肌肉蛋白，这些肌肉将更高水平的体育活动与更好的认知联系起来并减少赔率 老年人的痴呆症。多阶段分析将用于识别与a）物理的肌肉蛋白 活动和b）认知接近死亡。然后分析与两种表型相关的蛋白质，我们将 确定将体育活动与更好认知联系起来的蛋白质。