Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Alzheimers Dement. 2024 Jul;20(7):4401-4410. doi: 10.1002/alz.13808. Epub 2024 Jun 14.
TAR DNA-binding protein 43 (TDP-43) is a highly prevalent proteinopathy that is involved in neurodegenerative processes, including axonal damage. To date, no ante mortem biomarkers exist for TDP-43, and few studies have directly assessed its impact on neuroimaging measures utilizing pathologic quantification.
Ante mortem diffusion-weighted images were obtained from community-dwelling older adults. Regression models calculated the relationship between post mortem TDP-43 burden and ante mortem fractional anisotropy (FA) within each voxel in connection with the hippocampus, controlling for coexisting Alzheimer's disease and demographics.
Results revealed a significant negative relationship (false discovery rate [FDR] corrected p < .05) between post mortem TDP-43 and ante mortem FA in one cluster within the left medial temporal lobe connecting to the parahippocampal cortex, entorhinal cortex, and cingulate, aligning with the ventral subdivision of the cingulum. FA within this cluster was associated with cognition.
Greater TDP-43 burden is associated with lower FA within the limbic system, which may contribute to impairment in learning and memory.
Post mortem TDP-43 pathological burden is associated with reduced ante mortem fractional anisotropy. Reduced FA located in the parahippocampal portion of the cingulum. FA in this area was associated with reduced episodic and semantic memory. FA in this area was associated with increased inward hippocampal surface deformation.
TAR DNA 结合蛋白 43（TDP-43）是一种高度普遍的蛋白病变，参与神经退行性过程，包括轴突损伤。迄今为止，尚无 TDP-43 的生前生物标志物，并且很少有研究直接利用病理定量评估其对神经影像学测量的影响。
从居住在社区的老年人中获得了扩散加权图像。回归模型计算了死后 TDP-43 负担与海马体相关的每个体素的生前各向异性分数（FA）之间的关系，同时控制了并存的阿尔茨海默病和人口统计学因素。
结果显示，在与海马体相连的左内侧颞叶内的一个簇中，死后 TDP-43 与生前 FA 之间存在显著的负相关关系（经假发现率 [FDR]校正后 p<0.05），该簇与旁海马皮质、内嗅皮质和扣带相连，与扣带的腹侧分支一致。该簇内的 FA 与认知有关。
更高的 TDP-43 负担与边缘系统内的 FA 降低相关，这可能导致学习和记忆受损。
死后 TDP-43 病理负担与生前各向异性分数降低有关。位于扣带旁海马部分的 FA 减少。该区域的 FA 与情节和语义记忆减少有关。该区域的 FA 与向内的海马表面变形增加有关。
