INTRODUCTIONIn the aging brain, cognitive abilities emerge from the coordination of complex pathways arising from a balance between protective lifestyle and environmental factors and accumulation of neuropathologies.METHODSAs part of the Rush Memory and Aging Project (n = 440), we measured accelerometer‐based actigraphy, cognitive performance, and after brain autopsy, selected reaction monitoring mass spectrometry. Multilevel network analysis was used to examine the relationships among the molecular machinery of vesicular neurotransmission, Alzheimer's disease (AD) neuropathology, cognition, and late‐life physical activity.RESULTSSynaptic peptides involved in neuronal secretory function were the most influential contributors to the multilayer network, reflecting the complex interdependencies among AD pathology, synaptic processes, and late‐life cognition. Older adults with lower physical activity evidenced stronger adverse relationships among phosphorylated tau peptides, markers of synaptic integrity, and tangle pathology.DISCUSSIONNetwork‐based approaches simultaneously model interdependent biological processes and advance understanding of the role of physical activity in age‐associated cognitive impairment.Highlights Network‐based approaches simultaneously model interdependent biological processes. Secretory synaptic peptides were influential contributors to the multilayer network. Older adults with lower physical activity had adverse relationships among pathology. There was interdependence among phosphorylated tau, synaptic integrity, and tangles. Network methods elucidate the role of physical activity in cognitive impairment.

中文翻译：

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阿尔茨海默病发病机制的多层网络分析：p-tau、突触肽和身体活动的作用


引言在衰老的大脑中，认知能力来自保护性生活方式和环境因素之间的平衡以及神经病理学积累所产生的复杂通路的协调。方法作为 Rush Memory and Aging Project （n = 440） 的一部分，我们测量了基于加速度计的活动记录仪、认知表现，并在脑尸检后选择了反应监测质谱法。多层次网络分析用于检查囊泡神经传递的分子机制、阿尔茨海默病 （AD） 神经病理学、认知和晚年身体活动之间的关系。结果参与神经元分泌功能的动力学肽是多层网络最有影响力的贡献者，反映了 AD 病理学、突触过程和晚年认知之间复杂的相互依赖关系。体力活动较少的老年人证明磷酸化 tau 肽、突触完整性标志物和缠结病理之间的不良关系更强。讨论基于网络的方法同时对相互依赖的生物过程进行建模，并促进对身体活动在与年龄相关的认知障碍中的作用的理解。亮点 基于网络的方法同时对相互依赖的生物过程进行建模。分泌型突触肽是多层网络的有影响力贡献者。体力活动较少的老年人在病理学之间存在不良关系。磷酸化 tau 、突触完整性和缠结之间存在相互依赖性。网络方法阐明了身体活动在认知障碍中的作用。