Kii amyotrophic lateral sclerosis (ALS) is a unique disease that occurs in the southern portion of the Kii Peninsula and exhibits a dual pathology of TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy and tauopathy. The incidence of ALS in this region was very high in the 1960s, briefly decreased through the 1980s, but began increasing again after 2000 with a change of high-concentration geographic foci. It is unclear, however, whether the unique pathological features have changed along with the incidence changes. This study analyzed postmortem specimens from neuropathologically confirmed Kii ALS cases from the 1970s (n = 4) and those after 1999 (n = 12) from the southern Kii Peninsula or outside of the area. Our results confirm the continued occurrence of Kii ALS after 2000 in the southern Kii Peninsula and the preservation of disease-specific neuronal tau pathology, including the widespread occurrence throughout the brain and spinal cord, sparse neuropil threads, and predominance in superficial layers. Furthermore, we assessed the glial tau pathology of Kii and non-Kii ALS in accordance with the aging-related tau astrogliopathy classification method for the first time and detected a unique brainstem predominant appearance of gray matter aging-related tau astrogliopathy in Kii ALS cases, which may provide clues to pathogenetic mechanisms.

中文翻译：

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2000 年代后 Kii 肌萎缩侧索硬化症的持续存在及其特征性的衰老相关 tau 星形胶质细胞病

纪伊肌萎缩侧索硬化症 (ALS) 是一种发生在纪伊半岛南部的独特疾病，表现出 43 kDa (TDP-43) 蛋白病和 tau 蛋白病的 TAR DNA 结合蛋白双重病理学。该地区 ALS 的发病率在 20 世纪 60 年代非常高，在 1980 年代短暂下降，但在 2000 年之后随着高集中地理病灶的变化又开始增加。然而，尚不清楚独特的病理特征是否随着发病率的变化而改变。这项研究分析了 20 世纪 70 年代（n = 4）和 1999 年后（n = 12）来自纪伊半岛南部或该地区以外经神经病理学证实的纪伊 ALS 病例的尸检标本。我们的结果证实了 2000 年之后 Kii ALS 在纪伊半岛南部持续发生，并且保留了疾病特异性神经元 tau 病理学，包括在整个大脑和脊髓中广泛发生、稀疏的神经纤维丝以及在浅层中占主导地位。此外，我们首次根据衰老相关 tau 星形胶质病分类方法评估了 Kii 和非 Kii ALS 的神经胶质 tau 病理学，并在 Kii ALS 病例中检测到灰质衰老相关 tau 星形胶质病的独特脑干主要表现，这可能为发病机制提供线索。