Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment
Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment
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DOI：
10.1523/jneurosci.0704-15.2015
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发表时间：
2015-07-15
影响因子：
5.3
通讯作者：
Maestu, Fernando
中科院分区：
文献类型：
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作者：
Canuet, Leonides;Pusil, Sandra;Maestu, Fernando
突触功能障碍是阿尔茨海默病的核心缺陷，先于标志性病理异常。静息态脑磁图（MEG）用于评估功能连接模式（作为突触功能障碍的指标）是否与CSF生物标志物相关[即，磷酸化-tau（p-tau）和淀粉样蛋白β（A β 42）水平]。我们研究了12名被诊断患有阿尔茨海默病导致的轻度认知障碍的人类受试者，比较了CSF中生物标志物水平正常和异常的受试者。我们还评估了异常的功能连接和结构连接异常之间的关联，用扩散张量成像测量，以及认知缺陷和CSF变量对网络紊乱的会聚影响。在2.5年的随访期间，三分之一的患者转化为阿尔茨海默病。CSF p-tau和A β 42水平异常的患者表现出功能连接性降低和增加，影响边缘系统结构，如前/后扣带回皮质、眶额皮质和不同频带的内侧颞区。由p-tau介导的后扣带功能连接的减少与海马扣带轴突完整性受损相关。我们注意到，几个连接异常预测CSF生物标志物和认知评分。这些初步结果表明，早期阿尔茨海默病中淀粉样蛋白沉积和神经元损伤的CSF标记物与皮质网络破坏的双重模式相关，影响默认模式网络和颞叶皮质的关键区域。脑磁图是有用的，以检测早期突触功能障碍与阿尔茨海默氏病的脑病理功能网络组织。
Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (A beta 42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and A beta 42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization.