Coulborn Sean, Schafer Rhiana, Roy Ashlin R K, Sokolowski Andrzej, Cryns Noah G, Leichter Dana, Lago Argentina Lario, Ramos Eliana Marisa, Cobigo Yann, Spina Salvatore, Grinberg Lea T, Geschwind Daniel H, Gorno-Tempini Maria L, Kramer Joel H, Rosen Howard J, Miller Bruce L, Seeley William W, Perry David C
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Department of Neurology, University of California, Los Angeles, California, USA.
Ann Clin Transl Neurol. 2025 May;12(5):947-957. doi: 10.1002/acn3.70014. Epub 2025 Mar 10.
Certain frontotemporal lobar degeneration subtypes, including TDP-A and B, can either occur sporadically or in association with specific genetic mutations. It is uncertain whether syndromic or imaging features previously associated with these patient groups are subtype or genotype specific. Our study sought to discern the similarities and differences between sporadic and genetic TDP-A and TDP-B.
We generated individual atrophy maps and extracted mean atrophy scores for regions of interest-frontotemporal, occipitoparietal, thalamus, and cerebellum-in 54 patients with FTLD-TDP types A or B. We calculated asymmetry as the absolute difference in atrophy between right and left frontotemporal regions, and dorsality as the difference in atrophy between dorsal and ventral frontotemporal regions. We used ANCOVAs adjusted for disease severity to compare atrophy extent or imbalance, neuropsychological tests, and behavioral measures.
For some regions, volumetric differences were found either between TDP subtypes (e.g., worse occipitoparietal and cerebellum atrophy in TDP-A than B), or within subtypes depending on genetic status (e.g., worse thalamic and occipitoparietal atrophy in C9orf72-associated TDP-B than sporadic TDP-B). While progranulin mutation-associated TDP-A and sporadic TDP-A cases can be strongly asymmetric, TDP-A and TDP-B associated with C9orf72 tended to be symmetric. TDP-A was more dorsal in atrophy than TDP-B, regardless of genetic status.
While some neuroimaging features are FTLD-TDP subtype-specific and do not significantly differ based on genotype, other features differ between sporadic and genetic forms within the same subtype and could decrease accuracy of classification algorithms that group genetic and sporadic cases.
某些额颞叶变性亚型，包括TDP-A和TDP-B，可散发出现或与特定基因突变相关。此前与这些患者群体相关的综合征或影像学特征是否具有亚型或基因型特异性尚不确定。我们的研究旨在辨别散发性和遗传性TDP-A和TDP-B之间的异同。
我们为54例A或B型额颞叶痴呆伴TDP（FTLD-TDP）患者生成了个体萎缩图谱，并提取了感兴趣区域（额颞叶、枕顶叶、丘脑和小脑）的平均萎缩评分。我们将不对称性计算为左右额颞叶区域萎缩的绝对差异，将背侧性计算为背侧和腹侧额颞叶区域萎缩的差异。我们使用经疾病严重程度校正的协方差分析来比较萎缩程度或失衡、神经心理学测试和行为指标。
在某些区域，发现TDP亚型之间存在体积差异（例如，TDP-A的枕顶叶和小脑萎缩比TDP-B更严重），或者在亚型内根据基因状态存在差异（例如，与C9orf72相关的TDP-B的丘脑和枕顶叶萎缩比散发性TDP-B更严重）。虽然与原纤维蛋白突变相关的TDP-A和散发性TDP-A病例可能存在强烈不对称，但与C9orf72相关的TDP-A和TDP-B往往是对称的。无论基因状态如何，TDP-A的萎缩比TDP-B更偏向背侧。
虽然一些神经影像学特征是FTLD-TDP亚型特异性的，且基于基因型没有显著差异，但同一亚型内散发性和遗传性形式之间的其他特征存在差异，这可能会降低对遗传和散发病例进行分组的分类算法的准确性。
