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晚期NC阶段3:一个诊断标签,以区分严重的LATE-NC和FTLD-TDP

Ryan K Shahidehpour^1,2, Yuriko Katsumata^1,3, Dennis W Dickson⁴

¹Sanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.

Acta neuropathologica

|April 28, 2025

概括

一个新的诊断标签可靠地区分了临主导的与年龄相关的TDP-43脑病变神经病理变化 (LATE-NC) 阶段3和带有TDP-43内含的前叶退化 (FTLD-TDP). 该标题有助于对TDP-43蛋白病变进行分类,提高了诊断准确度.

科学领域:

神经病理学神经病理学
神经退行性疾病神经退行性疾病
TDP-43 蛋白质病变蛋白质病变

背景情况:

区分临主导的与年龄相关的TDP-43脑病变神经病变变化 (LATE-NC) 和带有TDP-43入的前叶退化 (FTLD-TDP) 是具有挑战性的,特别是在LATE-NC第3阶段,因为TDP-43病理在中额头 (MFG).
TDP-43蛋白质病变是认知衰退和痴呆症的重要原因,需要准确的诊断标准.

研究的目的:

开发和验证诊断标签,以区分LATE-NC第3阶段与FTLD-TDP和其他TDP-43蛋白病变.
调查与LATE-NC 第三阶段相关的临床和遗传特征.

主要方法:

在大脑银行队列中分析TDP-43蛋白病变 (肯塔基大学,90+研究,梅奥诊所).
使用数字病理学和手动计数方法量化病理负担.
来自NACC和ADGC的临床和遗传数据的评估,包括GRN,TMEM106B和APOE变种.

主要成果:

一个数据驱动的标题成功地将90%以上的案例分类为LATE-NC第3阶段或FTLD-TDP.
确定了诊断上具有挑战性的场景,包括FTLD-TDP Type B和一个新的TDP-43亚型.
发现GRN (rs5848) 风险等位基因与LATE-NC 第3阶段的优先关联,但没有TMEM106B或APOE变异.

结论:

为LATE-NC 3期和FTLD-TDP开发了一种可靠的诊断标签,改进了TDP-43蛋白病变的分类.
该标题考虑了潜在的诊断陷,增强了神经病理学评估.
基因分析表明与LATE-NC阶段3的特定等位基因关联,需要进一步调查.

关键词:

这就是ALS.阿尔塔格 (ARTAG) 是一个古老的城市.这是一个FTLD-MND.在LNT LNT.扫描仪 (ScanScope) 是一个扫描仪.1990年6月22日美国

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