Department of Neurology, Penn Frontotemporal Degeneration Center, Philadelphia, PA, USA..
Department of Neurology, Penn Frontotemporal Degeneration Center, Philadelphia, PA, USA.
Neurobiol Aging. 2022 May;113:95-107. doi: 10.1016/j.neurobiolaging.2022.02.007. Epub 2022 Feb 24.
Frontotemporal lobar degeneration (FTLD) includes clinically similar FTLD-tau or FTLD-TDP proteinopathies which lack in vivo markers for accurate antemortem diagnosis. To identify early distinguishing sites of cortical atrophy between groups, we retrospectively analyzed in vivo volumetric MRI from 42 FTLD-Tau and 21 FTLD-TDP patients and validated these findings with postmortem measures of pathological burden. Our frequency-based staging model revealed distinct loci of maximal early cortical atrophy in each group, including dorsolateral and medial frontal regions in FTLD-Tau and ventral frontal and anterior temporal regions in FTLD-TDP. Sørenson-Dice calculations between proteinopathy groups showed little overlap of phases. Conversely, within-group subtypes showed good overlap between 3R- and 4R-tauopathies, and between TDP-43 Types A and C for early regions with subtle divergence between subtypes in subsequent phases of atrophy. Postmortem validation found an association of imaging phases with pathologic burden within FTLD-tau (F = 17.44, p < 0.001) and FTLD-TDP (F = 42.32, p < 0.001). These results suggest that relatively early, distinct markers of atrophy may distinguish FTLD proteinopathies during life.
额颞叶变性（FTLD）包括临床上相似的 FTLD-tau 或 FTLD-TDP 蛋白病，它们缺乏准确的生前诊断标志物。为了确定两组之间皮质萎缩的早期区别部位，我们回顾性地分析了 42 例 FTLD-Tau 和 21 例 FTLD-TDP 患者的体内容积 MRI，并通过死后的病理负担测量对这些发现进行了验证。我们基于频率的分期模型揭示了每个组中最大的早期皮质萎缩的明显部位，包括 FTLD-Tau 的背外侧和内侧额叶区域以及 FTLD-TDP 的腹侧额叶和前颞叶区域。蛋白病组之间的 Sørensen-Dice 计算显示各阶段之间重叠较少。相反，在组内亚型中，3R- 和 4R-tauopathy 之间以及 TDP-43 类型 A 和 C 之间具有很好的重叠性，而在随后的萎缩阶段中，亚型之间的细微差异则表明早期区域的重叠性较好。尸检验证发现 FTLD-tau（F=17.44，p<0.001）和 FTLD-TDP（F=42.32，p<0.001）中影像学阶段与病理负担之间存在关联。这些结果表明，在生命过程中，相对早期、明显的萎缩标志物可能可以区分 FTLD 蛋白病。
