Tau-first subtype of Alzheimer's disease progression consistently identified through PET and CSF Neuroimaging: Understanding tau progression
Tau-first subtype of Alzheimer's disease progression consistently identified through PET and CSF Neuroimaging: Understanding tau progression
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通过 PET 和 CSF 神经影像一致鉴定出阿尔茨海默病进展的 Tau 第一个亚型：了解 tau 进展
DOI：
10.1002/alz.045412
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发表时间：
2020
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影响因子：
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通讯作者：
Aksman L
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文献类型：
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作者：
Aksman L
背景一些研究认为，一些阿尔茨海默病(AD)受试者在淀粉样变1、2之前就出现了早期的tau病变，这支持了一种假设，即在AD中存在多种不同的淀粉样亚型和tau病变进展。我们对这一假设进行了研究，将数据驱动的疾病亚型模型应用于淀粉样蛋白和tau PET以及脑脊液测量。第一项是基于tau-PET的分析，它使用了来自402名受试者的8个区域淀粉样蛋白PET(AV-45)SUVR和10个tau PET(AV-1451)SUVR，在同一次访问中进行了两次扫描。第二个是基于tau-csf的分析，用基于脑脊液的tau-PET SUVR预测(见图2)代替实际的tau-PET，提供了一个包含996名受试者的更大的数据集。我们使用亚型和分期推断(SuStaIn3)算法来推断疾病进展亚型和个人的疾病阶段，并表征亚型之间的人口统计学、认知和脑脊液差异。结果我们在基于tau-PET的分析中发现了两种基于PET的亚型：淀粉样蛋白优先亚型(84%的受试者)和tau优先亚型(16%的受试者)，其中Braak I-III期相关的tau SUVR(海马体、杏仁核、内嗅皮层)首先变得异常(图1A，B)。基于tau-CSF的分析证实了这些亚型：淀粉样蛋白优先(83%的受试者)和tau优先(17%的受试者；图2A，B)。在基于tau-PET的分析中，不同亚型之间的人口统计学或受试者阶段没有显著差异(图1C，D)。在基于tau-csf的分析中，年龄上有微小的差异(首先出现淀粉样蛋白的受试者年龄大2.4岁，Cohen‘s f2=0.02，p<；0.05)。首先患有淀粉样蛋白的患者的执行功能也稍差(Cohen‘s f2=0.02，p<；0.001；图3C)，并且如预期的那样，脑脊液淀粉样蛋白异常较多(Cohen’s f2=0.1，p<；0.001；图3D)，而tau-First患者的脑脊液tau异常更多(Cohen‘s f2=0.06，p<；0.001；图3D)。我们的数据驱动方法支持在淀粉样变之前存在tau积聚的AD亚型。参考文献：1.杜伊卡尔茨等人，2015年，《神经学学报》；2.Weigand等人，2019年，Brain Comm；3.Young等人，2018年，《自然通讯》。
BackgroundSeveral studies contend that some Alzheimer’s disease (AD) subjects develop early‐stage tau pathology before amyloid pathology1,2, supporting a hypothesis that there are multiple distinct subtypes of amyloid and tau pathology progression within AD. We investigated this hypothesis, applying data‐driven disease subtyping models to both amyloid and tau PET as well as CSF measures.MethodWe performed two separate analyses using cross‐sectional data from ADNI. The first was a tau‐PET‐based analysis, which used eight regional amyloid PET (AV‐45) SUVRs and ten tau PET (AV‐1451) SUVRs from 402 subjects with both scans at the same visit. The second was a tau‐CSF‐based analysis, substituting CSF‐based prediction of tau PET SUVR (see Figure 2) in place of actual tau PET to give a larger dataset of 996 subjects. We used the Subtype and Stage Inference (SuStaIn3) algorithm to infer disease progression subtypes and individuals’ disease stages, and characterized demographic, cognitive and CSF differences across subtypes.ResultWe found two PET‐based subtypes in the tau‐PET‐based analysis: an amyloid‐first (84% of subjects) subtype and a tau‐first (16% of subjects) subtype in which Braak stage I‐III related tau SUVRs (hippocampus, amygdala, entorhinal cortex) become abnormal first (Figure 1A,B). The tau‐CSF‐based analysis confirms these subtypes: amyloid‐first (83% of subjects) and tau‐first (17% of subjects; Figure 2A,B). There were no significant differences in demographics or subject stages between subtypes in the tau‐PET‐based analysis (Figure 1C,D). In the tau‐CSF‐based analysis there was a small difference in age (amyloid‐first subjects 2.4 years older, Cohen’s f2= 0.02, p < 0.05). Amyloid‐first individuals also had slightly worse executive function (Cohen’s f2= 0.02, p < 0.05; Figure 3C) and, as expected, more abnormal CSF amyloid (Cohen’s f2= 0.10, p < 0.001; Figure 3D) while tau‐first individuals had more abnormal CSF tau (Cohen’s f2= 0.06, p < 0.001; Figure 3D).ConclusionWe identified amyloid‐first and tau‐first AD subtypes consistently across PET and CSF biomarkers. Our data‐driven approach supports the existence of a subtype of AD with tau accumulation prior to amyloid pathology. References: 1. Duyckaerts, et al., 2015, Acta Neuropath; 2. Weigand, et al., 2019, Brain Comm; 3. Young, et al., 2018, Nature Comm.