Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Neuropathol Appl Neurobiol. 2021 Dec;47(7):931-941. doi: 10.1111/nan.12710. Epub 2021 Apr 7.
This study aimed to clarify the different topographical distribution of tau pathology between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and establish a machine learning-based decision tree classifier.
Paraffin-embedded sections of the temporal cortex, motor cortex, caudate nucleus, globus pallidus, subthalamic nucleus, substantia nigra, red nucleus, and midbrain tectum from 1020 PSP and 199 CBD cases were assessed by phospho-tau immunohistochemistry. The severity of tau lesions (i.e., neurofibrillary tangle, coiled body, tufted astrocyte or astrocytic plaque, and tau threads) was semi-quantitatively scored in each region. Hierarchical cluster analysis was performed using tau pathology scores. A decision tree classifier was made with tau pathology scores using 914 cases. Cross-validation was done using 305 cases. An additional ten cases were used for a validation study.
Cluster analysis displayed two distinct clusters; the first cluster included only CBD, and the other cluster included all PSP and six CBD cases. We built a decision tree, which used only seven decision nodes. The scores of tau threads in the caudate nucleus were the most decisive factor for predicting CBD. In a cross-validation, 302 out of 305 cases were correctly diagnosed. In the pilot validation study, three investigators made a correct diagnosis in all cases using the decision tree.
Regardless of the morphology of astrocytic tau lesions, semi-quantitative tau pathology scores in select brain regions are sufficient to distinguish PSP and CBD. The decision tree simplifies neuropathologic differential diagnosis of PSP and CBD.
本研究旨在阐明额颞叶痴呆(FTLD)和皮质基底节变性(CBD)之间 tau 病理学的不同拓扑分布,并建立基于机器学习的决策树分类器。
对 1020 例 PSP 和 199 例 CBD 病例的颞叶皮质、运动皮质、尾状核、苍白球、丘脑底核、黑质、红核和中脑顶盖石蜡包埋切片进行磷酸化 tau 免疫组织化学染色。在每个区域对 tau 病变的严重程度(即神经纤维缠结、卷曲体、丛状星形胶质细胞或星形胶质斑块和 tau 丝)进行半定量评分。使用 tau 病理学评分进行层次聚类分析。使用 914 例病例的 tau 病理学评分制作决策树分类器。使用 305 例病例进行交叉验证。另外 10 例用于验证研究。
聚类分析显示出两个截然不同的簇;第一个簇仅包含 CBD,另一个簇包含所有 PSP 和 6 例 CBD。我们构建了一个决策树,仅使用了 7 个决策节点。尾状核中 tau 丝的评分是预测 CBD 的最决定性因素。在交叉验证中,305 例中的 302 例得到正确诊断。在初步验证研究中,三位研究者使用决策树对所有病例进行了正确诊断。
无论星形胶质细胞 tau 病变的形态如何,选择脑区的 tau 病理学半定量评分足以区分 PSP 和 CBD。决策树简化了 PSP 和 CBD 的神经病理学鉴别诊断。