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Abstract：
Association between the transactive response DNA-binding protein of 43 kDa (TDP-43), its newly described types (type α/type β), and resilience to Alzheimer\'s disease neuropathological change (ADNC) defined as preservation of normal cognitive functioning despite advanced ADNC has been evaluated in this case-control study of 63 older adults. Twenty-one resilient to ADNC individuals were matched 1:2 to nonresilient (Alzheimer\'s dementia) using propensity scores, accounting for age at death, neuritic plaque density, and neurofibrillary tangle stage. Resilient and matched nonresilient participants were similar in terms of gender, apolipoprotein E ε4 carriership, education, occupation, AD, and other pathologies. Resilient participants had lower frequency of TDP-43 co-pathology compared to nonresilient (19% vs. 62%, p = 0.002). Among TDP-43-positive cases, TDP-43 type α inclusions were absent in resilient to ADNC participants and were dominant in matched nonresilient cases (65%, p = 0.03). TDP-43 and TDP-43 types appear to be one of the key pathological determinants of loss of cognitive resilience to ADNC and hence are important in the understanding of the clinical expression of ADNC.
摘要：
43kDa的反应性DNA结合蛋白（TDP-43）之间的关联，其新描述的类型(α型/β型)，在这项对63名老年人进行的病例对照研究中，评估了对阿尔茨海默病神经病理学变化（ADNC）的弹性，ADNC定义为尽管晚期ADNC仍保持正常认知功能。21名具有ADNC弹性的个体使用倾向评分1:2与非弹性（阿尔茨海默氏症）进行匹配，考虑死亡年龄，神经炎性斑块密度，和神经原纤维缠结阶段。弹性和匹配的非弹性参与者在性别方面相似，载脂蛋白Eε4载体，教育,职业,AD,和其他病症。与非弹性相比，弹性参与者的TDP-43共病频率较低(19%vs.62%,p=0.002)。在TDP-43阳性病例中，TDP-43型α包涵体对ADNC参与者没有弹性，在匹配的非弹性病例中占主导地位(65%，p=0.03)。TDP-43和TDP-43类型似乎是ADNC认知弹性丧失的关键病理决定因素之一，因此对于理解ADNC的临床表现很重要。
