In Vivo Cortical Spreading Pattern of Tau and Amyloid in the Alzheimer Disease Spectrum
In Vivo Cortical Spreading Pattern of Tau and Amyloid in the Alzheimer Disease Spectrum
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DOI：
10.1002/ana.24711
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发表时间：
2016-08-01
影响因子：
11.2
通讯作者：
Lyoo, Chul Hyoung
中科院分区：
文献类型：
--
作者：
Cho, Hanna;Choi, Jae Yong;Lyoo, Chul Hyoung
目的：确定tau蛋白和淀粉样蛋白在体内皮层的扩散模式，并建立基于正电子发射断层扫描（PET）图像的阿尔茨海默病（AD）谱系中tau蛋白的分期。方法：我们纳入了195名参与者（53名AD， 52名遗忘性轻度认知障碍[MCI]， 23名非遗忘性MCI和67名健康对照），他们接受了2次PET扫描（F-18-florbetaben用于淀粉样蛋白- β和f -18- af -1451用于tau）。我们假设，早期病理表现的区域可能在更多的参与者中显示出增加的结合，并通过分类受累的区域频率获得tau积累的传播顺序。我们根据每个阶段复合区域的Z分数将每个参与者分为基于图像的tau阶段。结果：在内侧颞区最常观察到Tau积累，并逐步扩散到基底和外侧颞、下顶叶、后扣带和其他关联皮质，然后最终扩散到初级皮质区。相反，在弥漫性新皮质区发现淀粉样蛋白积累的频率相似，然后最终扩散到内侧颞区。基于图像的tau阶段与一般认知状态相关，而皮层变薄仅在晚期tau阶段发现：内侧颞区在V期，广泛的皮层在vi期。解释：我们的PET研究复制了tau和淀粉样蛋白病理的死后扩散模式。与淀粉样蛋白在整个新皮层的弥漫性积累不同，tau蛋白的扩散是通过网络逐步发生的。基于图像的tau分期可能有助于客观评估AD的进展。
Objective: To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image-based tau staging in the Alzheimer disease (AD) spectrum.Methods: We included 195 participants (53 AD, 52 amnestic mild cognitive impairment [MCI], 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans (F-18-florbetaben for amyloid-beta and F-18-AV-1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image-based tau stage based on the Z score of the composite region for each stage.Results: Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image-based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI.Interpretation: Our PET study replicated postmortem spreading patterns of tau and amyloid-beta pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image-based tau staging may be useful for the objective assessment of AD progression.