Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally.

Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally).

Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions.

Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

尸检研究表明，局灶性前颞叶 (ATL) 神经变性最常由额颞叶变性 TDP-43 C 型病理引起。临床上，根据主要症状是否影响语言、物体的语义知识或影响，这些患者被用不同的术语描述，例如语义变异型原发性进行性失语症（svPPA）、语义痴呆（SD）或右颞叶变异型额颞叶痴呆（FTD）。人，或社会情感行为。 ATL 萎缩表现为不同程度的偏侧化，右侧病例被认为较为罕见，尽管由于缺乏充分表征、经过病理学验证的队列研究，对其患病率的估计受到阻碍。此外，尚不清楚左变体和右变体在 ATL 横截面和纵向上是否表现出相似的萎缩分布。

在这里，我们研究了迄今为止最大的一组经病理学证实的 TDP-43-C 病例，这些病例在生前被诊断为 svPPA、SD 或右颞叶变异 FTD。我们分析了 30 个病例的临床、认知和神经影像数据，其中一部分进行了纵向随访。在最近的结构和功能分割研究的指导下，我们构建了四个双边 ATL 感兴趣区域 (ROI)。萎缩侧化指数的计算可以比较两个半球之间的萎缩模式。这导致基于成像的病例自动分类为左侧为主或右侧为主。然后，我们比较了两组 ATL ROI 内的区域萎缩模式（横向）和萎缩进展（纵向）。

结果显示，40% 经病理证实患有颞叶变异的 TDP-43-C 病例表现为右侧萎缩。此外，我们的 ATL ROI 分析结果表明，无论萎缩偏侧化如何，两个 ATL 内的萎缩分布都遵循从内侧到外侧的梯度。最后，在左侧和右侧病例中，萎缩似乎都进展到对侧 ATL，并从前颞极发展到后颞和眶额区域。

综上所述，我们的研究结果表明，早期以右侧为主的 ATL 萎缩在 TDP-43-C 病理学中很常见，并且 ATL 内损伤的分布在左侧和右侧变异中似乎相同。因此，无论临床表型和萎缩侧化有何差异，FTD 的两种时间变异都应被视为同一疾病的谱系表现。