The A/T/N model applied through imaging biomarkers in a memory clinic
The A/T/N model applied through imaging biomarkers in a memory clinic
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DOI：
10.1007/s00259-019-04536-9
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发表时间：
2019-12-02
影响因子：
9.1
通讯作者：
Garibotto, Valentina
中科院分区：
文献类型：
--
作者：
Dodich, Alessandra;Mendes, Aline;Garibotto, Valentina
目的A/T/N模型是研究阿尔茨海默病（Alzheimer's disease，AD）病理基础的一种研究框架。淀粉样变性A、神经纤维缠结T和神经变性N）。该系统在临床人群中的应用仍然有限。本研究的目的是通过18F-flortaucipir PET评价T分布与A和N的关系，并通过记忆诊所患者的成像生物标志物描述A/T/N状态。方法对81例有主、客观认知功能障碍的患者，采用正电子发射断层扫描（PET）和结构磁共振成像（MRI），将其分为A+/A-和N+/N-两类。在体素水平上跨A/N亚组比较Tau沉积。T状态通过基于A/N亚组的总体临界点定义，受试者按照A/T/N模型进行分类。结果A+N+和A+N-亚组的tau蛋白含量均高于A-N-亚组，其中A+N-亚组的tau蛋白沉积主要局限于颞叶内侧和外侧。总体分界点区分A+N+和A+N-与A-N-受试者。在A/T/N分类中，23%的患者显示阴性生物标志物特征，58%属于阿尔茨海默氏症连续体，19%的样本以非AD病理变化为特征。结论颞叶内侧区和外侧区是A+受试者中tau蛋白聚集的重要部位，可能是早期临床变化的有用标志。这是首次在记忆临床人群中使用18 F-flortaucipir PET应用A/T/N模型的研究。大多数患者显示出与阿尔茨海默氏症连续体一致的特征，而一小部分患者显示出提示可能的其他神经退行性疾病的特征。这些结果支持了A/T/N模型在临床实践中的适用性。
Purpose The A/T/N model is a research framework proposed to investigate Alzheimer's disease (AD) pathological bases (i.e., amyloidosis A, neurofibrillary tangles T, and neurodegeneration N). The application of this system on clinical populations is still limited. The aim of the study is to evaluate the topography of T distribution by 18F-flortaucipir PET in relation to A and N and to describe the A/T/N status through imaging biomarkers in memory clinic patients. Methods Eighty-one patients with subjective and objective cognitive impairment were classified as A+/A- and N+/N- through amyloid PET and structural MRI. Tau deposition was compared across A/N subgroups at voxel level. T status was defined through a global cut point based on A/N subgroups and subjects were categorized following the A/T/N model. Results A+N+ and A+N- subgroups showed higher tau burden compared to A-N- group, with A+N- showing significant deposition limited to the medial and lateral temporal regions. Global cut point discriminated A+N+ and A+N- from A-N- subjects. On A/T/N classification, 23% of patients showed a negative biomarker profile, 58% fell within the Alzheimer's continuum, and 19% of the sample was characterized by non-AD pathologic change. Conclusion Medial and lateral temporal regions represent a site of significant tau accumulation in A+ subjects and possibly a useful marker of early clinical changes. This is the first study in which the A/T/N model is applied using 18F-flortaucipir PET in a memory clinic population. The majority of patients showed a profile consistent with the Alzheimer's continuum, while a minor percentage showed a profile suggestive of possible other neurodegenerative diseases. These results support the applicability of the A/T/N model in clinical practice.