Transactive response DNA-binding protein 43 (TDP-43) pathology is categorized as type A-E in frontotemporal lobar degeneration and as type α-β in Alzheimer disease (AD) based on inclusion type. We screened amygdala slides of 131 cases with varying ages at death, clinical/neuroimaging findings, and AD neuropathologic changes for TDP-43 pathology using anti-phospho-TDP-43 antibodies. Seven cases (5%) only showed atypical TDP-43 inclusions that could not be typed. Immunohistochemistry and immunofluorescence assessed the atypical star-shaped TDP-43 pathology including its distribution, species, cellular localization, and colocalization with tau. All 7 had died at an extremely old age (median: 100 years [IQR: 94–101]) from nonneurological causes and none had dementia (4 cognitively unimpaired, 3 with amnestic mild cognitive impairment). Neuroimaging showed mild medial temporal involvement. Pathologically, the star-shaped TDP-43-positive inclusions were found in medial (subpial) amygdala and, occasionally, in basolateral regions. Hippocampus only showed TDP-43-positive neurites in the fimbria and subiculum while the frontal lobe was free of TDP-43 inclusions. The star-shaped inclusions were better detected with antibodies against N-terminal than C-terminal TDP-43. Double-labeling studies confirmed deposition of TDP-43 within astrocytes and colocalization with tau. We have identified a novel TDP-43 pathology with star-shaped morphology associated with superaging, with a homogeneous clinicopathologic picture, possibly representing a novel, true aging-related TDP-43 pathology.

中文翻译：

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最年长老人新型星形反应反应 DNA 结合蛋白 43 (TDP-43) 病理学的临床病理特征


根据包涵体类型，交互反应 DNA 结合蛋白 43 (TDP-43) 病理学在额颞叶变性中被分类为 A-E 型，在阿尔茨海默病 (AD) 中被分类为 α-β 型。我们使用抗磷酸 TDP-43 抗体筛选了 131 例不同死亡年龄患者的杏仁核切片、临床/神经影像学结果和 AD 神经病理学变化的 TDP-43 病理学。 7 例 (5%) 仅显示无法分型的非典型 TDP-43 包涵体。免疫组织化学和免疫荧光评估了非典型星形 TDP-43 病理学，包括其分布、种类、细胞定位以及与 tau 的共定位。所有 7 人均因非神经原因而去世，年龄极高（中位值：100 岁 [IQR：94-101]），并且没有人患有痴呆症（4 人没有认知障碍，3 人患有遗忘性轻度认知障碍）。神经影像显示轻度内侧颞叶受累。病理学上，星形 TDP-43 阳性包涵体发现于内侧（软膜下）杏仁核，偶尔也发现于基底外侧区域。海马仅在海马伞和下托中显示出 TDP-43 阳性神经突，而额叶则没有 TDP-43 包涵体。使用抗 N 端 TDP-43 的抗体比抗 C 端 TDP-43 的抗体能更好地检测到星形内含物。双标记研究证实了 TDP-43 在星形胶质细胞内沉积并与 tau 蛋白共定位。我们已经确定了一种新的 TDP-43 病理学，其具有与超衰老相关的星形形态，具有均匀的临床病理学图片，可能代表一种新颖的、真正的与衰老相关的 TDP-43 病理学。