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

项目总结 目前还没有有效的治疗方法来减少病理性阿尔茨海默病(AD)和 老年人口中认知功能减退和阿尔茨海默病的相关病理。而两者之间的联系 体力活动和认知是有充分证据的，其认知益处背后的分子机制 目前还没有确定。这一知识差距是预防AD的体力活动干预的障碍 和相关痴呆(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 从已故的特征良好的老年参与者的肌肉样本投射到记忆和衰老 拉什阿尔茨海默病中心的项目发现老年人受体育活动影响的肌肉蛋白质 并识别可能将更高水平的体力活动与更好的认知和减少联系在一起的蛋白质 死亡前患痴呆症的几率。 拟议的项目将利用来自记忆和老龄化项目的现有数据和生物样本，包括 每年一次的认知和运动测试，自我报告病史和体力活动。定量物理 活动指标是从日常生活中戴在手腕上的监视器上的多天录音中提取出来的。脑区 ADRD病理指标收集自尸检死者和冰冻的股四头肌 是可用的。该项目有两个目标： 1)量化来自特征良好的老年人的死后股四头肌肌肉样本(N=500)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进行相关研究 定量测定股四头肌样本中的~8000个蛋白质。 2)确定将高水平的体力活动与更好的认知和更低的几率联系在一起的肌肉蛋白质 老年人患痴呆症的风险。将使用多阶段分析来识别与a)身体相关的肌肉蛋白质。 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，我们将 确定将体力活动与更好的认知联系起来的蛋白质。

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.