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用于减少病理性阿尔茨海默病（AD）的后果， 在我们的老龄化人群中认知能力下降和AD痴呆的相关病理学。虽然两者之间的联系 体力活动和认知是有据可查的，其认知益处的分子机制 尚未被确认。这种知识差距是身体活动干预预防AD的障碍 及相关痴呆（ADRD）和老年认知能力下降。 这项拟议的补充将应用MoTrPAC开发的大规模肌肉蛋白质组学平台 项目的肌肉样本，从已故的特点良好的老年参与者的记忆和衰老 拉什阿尔茨海默病中心的项目，以发现老年人身体活动影响的肌肉蛋白 成年人，并确定蛋白质，这些蛋白质可能将更高水平的体力活动与更好的认知能力联系起来， 死亡前患痴呆症的几率 拟议的项目将利用记忆和衰老项目的现有数据和生物标本，包括 年度认知和运动测试，自我报告病史和身体活动。定量物理 在日常生活期间，从来自腕戴式监视器的多日记录中提取活动度量。大脑 ADRD病理学指标收集自进行尸检的死亡动物和冷冻的股四头肌 服务器租用-美国服务租用该项目有两个目标： 1)对来自特征良好的老年人的死后股四头肌样本（N = 500）中的蛋白质组进行定量 成年人了应用MoTrPAC项目开发的大规模肌肉蛋白质组学平台， 四头肌样品中约8，000种蛋白质的定量。 2)确定肌肉蛋白质，将更高水平的体力活动与更好的认知和更低的几率联系起来 老年痴呆症一个多阶段的分析将用于确定肌肉蛋白质相关的a）物理 活动和B）接近死亡的认知。然后分析与这两种表型相关的蛋白质， 确定将身体活动与更好的认知联系起来的蛋白质。