Functional connectivity associated with tau levels in ageing, Alzheimer's, and small vessel disease
Functional connectivity associated with tau levels in ageing, Alzheimer's, and small vessel disease
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DOI：
10.1093/brain/awz026
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发表时间：
2019-04-01
期刊：
影响因子：
14.5
通讯作者：
Ewers, Michael
中科院分区：
文献类型：
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作者：
Franzmeier, Nicolai;Rubinski, Anna;Ewers, Michael
在阿尔茨海默氏病中，tau病理在整个皮质中从颞下叶延伸，随之而来的认知下降和痴呆症。同样，在正常衰老和小血管疾病中也观察到了限定的病理性tau模式，这表明在正常衰老和不同疾病中，tau病理的空间有序分布分布。体外发现表明，病理性的tau可能以活性依赖性方式传播神经元连接。支持这一概念，功能性大脑网络显示出与TAU沉积模式的空间对应关系。但是，尚不清楚较高的网络连通性是否促进了tau的传播。为了解决这个问题，我们包括55名正常老年人（即认知正常，淀粉样蛋白阴性），50名阿尔茨海默氏病患者（即淀粉样蛋白阳性）涵盖痴呆症谱系的症状，以及36例纯净患者（即淀粉样淀粉样蛋白阴性）患者小血管疾病引起的血管认知障碍。用AV1451 tau-pet和静止状态功能MRI评估所有受试者。在每个组中，我们计算了基于ATLAS的静止状态功能MRI功能连接，涵盖了整个新皮层的400个区域。使用相同的地图集，我们还在每个组中评估了400个感兴趣区域之间tau-pet水平的协方差。我们发现，较高的静止状态功能MRI评估了任何感兴趣区域对之间的功能连接性，与相应的感兴趣区域中Tau-pet结合的协方差较高。在正常衰老，阿尔茨海默氏病和血管认知障碍中一直发现这一结果。特别是，由最高的tau-pet吸收定义的下颞肉螺旋体在功能紧密连接的目标区域中显示出tau-pet水平的高预测值。无论存在痴呆症状（轻度认知障碍或痴呆症），淀粉样蛋白沉积（通过淀粉样蛋白-PET评估）或小血管疾病，检测到功能连通性与TAU-PET吸收之间的这些关联。我们的发现表明，大脑区域之间的更高功能连通性与共享的tau级相关，支持神经活动促进的类似prion的tau散布的观点。
In Alzheimer's disease, tau pathology spreads hierarchically from the inferior temporal lobe throughout the cortex, ensuing cognitive decline and dementia. Similarly, circumscribed patterns of pathological tau have been observed in normal ageing and small vessel disease, suggesting a spatially ordered distribution of tau pathology across normal ageing and different diseases. In vitro findings suggest that pathological tau may spread 'prion-like' across neuronal connections in an activity-dependent manner. Supporting this notion, functional brain networks show a spatial correspondence to tau deposition patterns. However, it remains unclear whether higher network-connectivity facilitates tau propagation. To address this, we included 55 normal aged elderly (i.e. cognitively normal, amyloid-negative), 50 Alzheimer's disease patients (i.e. amyloid-positive) covering the preclinical to dementia spectrum, as well as 36 patients with pure (i.e. amyloid-negative) vascular cognitive impairment due to small vessel disease. All subjects were assessed with AV1451 tau-PET and resting-state functional MRI. Within each group, we computed atlas-based resting-state functional MRI functional connectivity across 400 regions of interest covering the entire neocortex. Using the same atlas, we also assessed within each group the covariance of tau-PET levels among the 400 regions of interest. We found that higher resting-state functional MRI assessed functional connectivity between any given region of interest pair was associated with higher covariance in tau-PET binding in corresponding regions of interest. This result was consistently found in normal ageing, Alzheimer's disease and vascular cognitive impairment. In particular, inferior temporal tau-hotspots, as defined by highest tau-PET uptake, showed high predictive value of tau-PET levels in functionally closely connected regions of interest. These associations between functional connectivity and tau-PET uptake were detected regardless of presence of dementia symptoms (mild cognitive impairment or dementia), amyloid deposition (as assessed by amyloid-PET) or small vessel disease. Our findings suggest that higher functional connectivity between brain regions is associated with shared tau-levels, supporting the view of prion-like tau spreading facilitated by neural activity.