Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Pharmacology, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Basque Country (EHU/UPV), Leioa, Spain.
Alzheimers Dement. 2024 Nov;20(11):8012-8027. doi: 10.1002/alz.14286. Epub 2024 Oct 12.
In 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.
As 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.
Synaptic 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.
Network-based approaches simultaneously model interdependent biological processes and advance understanding of the role of physical activity in age-associated cognitive impairment.
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.
在衰老的大脑中，认知能力源自于保护生活方式和环境因素与神经病理学积累之间平衡的复杂途径的协调。
作为 Rush 记忆与衰老项目的一部分（n=440），我们测量了基于加速度计的活动记录仪、认知表现，以及大脑尸检后，选择反应监测质谱法。多层次网络分析用于研究囊泡神经传递的分子机制、阿尔茨海默病（AD）病理学、认知和晚年体力活动之间的关系。
参与神经元分泌功能的突触肽是多层网络中最具影响力的贡献者，反映了 AD 病理学、突触过程和晚年认知之间的复杂相互依存关系。体力活动较少的老年人中，磷酸化 tau 肽、突触完整性标志物和缠结病理学之间存在更强的不利关系。
基于网络的方法同时对相互依存的生物过程进行建模，并深入了解体力活动在与年龄相关的认知障碍中的作用。
基于网络的方法同时对相互依存的生物过程进行建模。分泌性突触肽是多层网络中的重要贡献者。体力活动较少的老年人中，病理之间存在不利关系。磷酸化 tau、突触完整性和缠结之间存在相互依存关系。网络方法阐明了体力活动在认知障碍中的作用。
