Vatsavayai Sarat C, Yoon Soo Jin, Gardner Raquel C, Gendron Tania F, Vargas Jose Norberto S, Trujillo Andrew, Pribadi Mochtar, Phillips Joanna J, Gaus Stephanie E, Hixson John D, Garcia Paul A, Rabinovici Gil D, Coppola Giovanni, Geschwind Daniel H, Petrucelli Leonard, Miller Bruce L, Seeley William W
1 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA.
2 Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, South Korea.
Brain. 2016 Dec;139(Pt 12):3202-3216. doi: 10.1093/brain/aww250. Epub 2016 Oct 22.
SEE SCABER AND TALBOT DOI101093/AWW264 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus. At autopsy, widespread RNA foci and dipeptide repeat protein inclusions were observed, but TDP-43 pathology was nearly absent, even in degenerating brain regions. Case 2 was a 74-year-old female with atypical frontotemporal dementia-motor neuron disease who underwent temporal lobe resection for epilepsy 5 years prior to her first frontotemporal dementia symptoms. Archival surgical resection tissue contained RNA foci, dipeptide repeat protein inclusions, and loss of nuclear TDP-43 but no TDP-43 inclusions despite florid TDP-43 inclusions at autopsy 8 years after first symptoms. These findings suggest that C9orf72-specific phenomena may impact brain structure and function and emerge before first symptoms and TDP-43 aggregation.
有关本文的科学评论，请参阅斯卡伯和塔尔博特的文献（DOI:10.1093/aww264）：C9orf72基因中的GGGGCC重复序列扩增导致额颞叶痴呆和/或肌萎缩侧索硬化。已发现多种病理特征，但其与疾病的相关性仍存在诸多争议。在此，我们描述了两名因C9orf72重复序列扩增导致额颞叶痴呆的具有启发性的患者。病例1是一名65岁女性，患有行为变异型额颞叶痴呆，伴有膝下前扣带回皮质、杏仁核和丘脑内侧枕核的局灶性变性。尸检时，观察到广泛的RNA病灶和二肽重复蛋白包涵体，但即使在脑变性区域，TDP-43病理几乎不存在。病例2是一名74岁女性，患有非典型额颞叶痴呆-运动神经元病，在首次出现额颞叶痴呆症状前5年因癫痫接受了颞叶切除术。存档的手术切除组织含有RNA病灶、二肽重复蛋白包涵体以及核TDP-43缺失，但在首次出现症状8年后尸检时，尽管有明显的TDP-43包涵体，但手术切除组织中未发现TDP-43包涵体。这些发现表明，C9orf72特异性现象可能影响脑结构和功能，并在首次症状和TDP-43聚集之前出现。
