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Abstract：
TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer\'s Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%). Regional TDP-43 pathologic assessment was available for 77% of participants, with hippocampus the most common region. Availability for the TDP-43-related measures increased over time, and was higher in centers with high proportions of participants with clinical FTLD. Part II: In 2142 participants with all TDP-43-related assessments available, 27% of participants had LATE-NC, whereas ALS-TDP or FTLD-TDP (ALS/FTLD-TDP) was present in 9% of participants, and 2% of participants had TDP-43 related to other pathologies (\"Other TDP-43\"). HS-A was present in 14% of participants, of whom 55% had LATE-NC, 20% ASL/FTLD-TDP, 3% Other TDP-43, and 23% no TDP-43. LATE-NC, ALS/FTLD-TDP, and Other TDP-43, were each associated with higher odds of dementia, HS-A, and hippocampal atrophy, compared to those without TDP-43 pathology. LATE-NC was associated with higher odds for Alzheimer\'s disease (AD) clinical diagnosis, AD neuropathologic change (ADNC), Lewy bodies, arteriolosclerosis, and cortical atrophy. ALS/FTLD-TDP was associated with higher odds of clinical diagnoses of primary progressive aphasia and behavioral-variant frontotemporal dementia, and cortical/frontotemporal lobar atrophy. When using NACC data for TDP-43-related analyses, researchers should carefully consider the incomplete availability of the different regional TDP-43 assessments, the high frequency of participants with ALS/FTLD-TDP, and the presence of other forms of TDP-43 pathology.
摘要：
TDP-43蛋白病是额颞叶变性（FTLD-TDP）子集的显着神经病理学特征，在肌萎缩侧索硬化症（ALS-TDP）中，和边缘占优势的年龄相关的TDP-43脑病神经病理变化（LATE-NC），并与衰老的海马硬化（HS-A）有关。我们在国家阿尔茨海默氏症协调中心（NACC）分两个部分检查了TDP-43相关的病理数据：（I）评估的可用性，和（II）在所有TDP-43措施可用的患者中，与临床诊断和其他神经病理学的关联。第一部分：4326名参与者使用包括TDP-43评估的表格收集神经病理学数据，HS-A(97%)和ALS(94%)的数据可用性最高，其次是FTLD-TDP（83％）。区域TDP-43病理评估可用于77%的参与者，海马是最常见的区域。TDP-43相关措施的可用性随着时间的推移而增加，并且在具有临床FTLD的参与者比例较高的中心中更高。第二部分：在2142名参与者中，所有与TDP-43相关的评估都可用，27％的参与者患有晚期NC，而ALS-TDP或FTLD-TDP（ALS/FTLD-TDP）存在于9%的参与者中，2%的参与者患有与其他病理相关的TDP-43（“其他TDP-43”）。14%的参与者存在HS-A，其中55%患有晚期NC，20%ASL/FTLD-TDP,3%其他TDP-43，23%无TDP-43。LATE-NC,ALS/FTLD-TDP,和其他TDP-43，都与较高的痴呆几率相关，HS-A,海马萎缩,与没有TDP-43病理的人相比。LATE-NC与阿尔茨海默病（AD）临床诊断的较高几率相关，AD神经病理变化（ADNC），路易体,动脉硬化，和皮质萎缩.ALS/FTLD-TDP与原发性进行性失语和行为变异额颞叶痴呆的临床诊断几率较高相关，和皮质/额颞叶萎缩。当使用NACC数据进行TDP-43相关分析时，研究人员应仔细考虑不同区域TDP-43评估的不完全可用性，ALS/FTLD-TDP参与者的频率较高，以及其他形式的TDP-43病理的存在。
