Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Department of Pathology, Stanford University, Stanford, CA, USA.
J Alzheimers Dis. 2018;66(4):1549-1558. doi: 10.3233/JAD-180162.
Transactive response binding protein-43 (TDP-43) cytoplasmic neuronal and glial aggregates (pathologic TDP-43) have been described in multiple brain diseases. We describe the associations between neuropathologically confirmed TDP-43 and cognition in two population-based cohorts: the Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS). In the HAAS, there was a significant association between hippocampal sclerosis (HS) and TDP-43 (OR = 11.04, p < 0.0001, 95% CI 3.57-34.13). In the NS, there were significant associations between TDP-43 and HS (OR = 16.44, p > 0.001 95%, CI 7.10-38.00) and Alzheimer's disease (AD) severity (OR = 1.74, p = 0.009, 95% CI 1.15-2.64). When cognitive scores were added to the model, HS remained significant but the other variables were not. When HS was removed from the model, the overall model remained significant and the associations between cognitive performance and TDP-43 (OR = 2.11, p = 0.022, 95% CI 1.11-4.02) were significant. In the NS, there was a significant association between cognitive performance and TDP-43 (OR 1.94 p = 0.005, 95% CI 1.22-3.09) (HS remained significant, but AD did not). When HS was removed from the model, only CERAD was significant (OR = 2.43 p < 0.001, 95% CI 1.58-3.74). These results support a consistent association between pathologic TDP-43, HS, and the development of cognitive impairment in two large studies of brain aging, while the relationship between AD pathology and TDP-43 may vary according to cohort-specific features.
转发性反应结合蛋白-43（TDP-43）细胞质神经元和神经胶质聚集物（病理性 TDP-43）已在多种脑部疾病中被描述。我们描述了在两个基于人群的队列中，神经病理学上确认的 TDP-43 与认知之间的关联：努恩研究（NS）和檀香山-亚洲老龄化研究（HAAS）。在 HAAS 中，海马硬化（HS）与 TDP-43 之间存在显著关联（OR=11.04，p<0.0001，95%CI 3.57-34.13）。在 NS 中，TDP-43 与 HS（OR=16.44，p>0.001 95%CI 7.10-38.00）和阿尔茨海默病（AD）严重程度（OR=1.74，p=0.009，95%CI 1.15-2.64）之间存在显著关联。当认知评分被添加到模型中时，HS 仍然显著，但其他变量则不显著。当从模型中删除 HS 时，整体模型仍然显著，并且认知表现与 TDP-43 之间的关联（OR=2.11，p=0.022，95%CI 1.11-4.02）仍然显著。在 NS 中，认知表现与 TDP-43 之间存在显著关联（OR 1.94，p=0.005，95%CI 1.22-3.09）（HS 仍然显著，但 AD 则不显著）。当从模型中删除 HS 时，只有 CERAD 仍然显著（OR=2.43，p<0.001，95%CI 1.58-3.74）。这些结果支持在两个大型脑老化研究中，病理性 TDP-43、HS 和认知障碍的发展之间存在一致的关联，而 AD 病理学与 TDP-43 之间的关系可能因队列的特定特征而异。
