Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease
Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease
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DOI：
10.1016/j.jalz.2019.03.006
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发表时间：
2019-07-01
影响因子：
14
通讯作者：
Younesi, Erfan
中科院分区：
文献类型：
--
作者：
Chiesa, Patrizia A.;Cavedo, Enrica;Younesi, Erfan
简介：人们对阿尔茨海默病风险个体的功能性大脑动力学的纵向轨迹和遗传风险因素的影响知之甚少。方法：在由 224 名阿尔茨海默病风险个体组成的大规模单中心队列中，对 2 年的两个连续时间点之间的默认模式网络 (DMN) 静息态功能连接 (FC) 进行了研究。结果：额叶和后区以及右侧显示了广泛的 DMN FC 变化海马体。没有横截面差异，然而，载脂蛋白 E epsilon 4 (APOE epsilon 4) 携带者表现出额叶 FC 增加较慢。个体大脑淀粉样蛋白负荷状态没有影响。讨论：我们首次证明 APOE epsilon 4 等位基因的多效性生物效应影响衰老过程中 DMN 的动态轨迹。动态功能生物标志物可能成为临床前靶向治疗干预措施开发的有用替代结果。 (C) 2019 年由爱思唯尔公司代表阿尔茨海默病协会发布。
Introduction: The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood.Methods: In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years.Results: Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E epsilon 4 (APOE epsilon 4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status.Discussion: For the first time, we demonstrated that the pleiotropic biological effect of the APOE epsilon 4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions. (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association.