University of Arizona College of Medicine, Phoenix, AZ, USA.
Acta Neuropathol. 2013 Jul;126(1):51-7. doi: 10.1007/s00401-013-1110-0. Epub 2013 Apr 20.
TAR DNA-binding protein 43 (TDP-43) has been heavily researched in recent years due to its involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Several studies have also sought to investigate the frequency of TDP-43 deposition in other neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, but there has been relatively little work focused on the prevalence, distribution and histopathological associations of abnormal TDP-43 deposits in the brains of cognitively normal elderly subjects. We screened thick, free-floating coronal sections of mesial temporal lobe from 110 prospectively followed and autopsied cognitively normal subjects (age range 71-100 years) using an immunohistochemical method for phosphorylated TDP-43. We found a 36.4 % prevalence of pathologic TDP-43, mostly in the form of neurites while perikaryal cytoplasmic neuronal inclusions were uncommon and intranuclear inclusions were rare. With respect to other concomitant pathologies commonly found in elderly individuals, cases with TDP-43 had a greater prevalence of argyrophilic grains (ARG) (40 vs. 18.6 %) and overall ARG density (moderate vs. sparse). There were no additional associations with other concomitant pathologies, including cerebral white matter rarefaction, incidental Lewy bodies, neurofibrillary tangles or amyloid plaques. These results indicate deposition of TDP-43 occurs in a substantial subset of cognitively normal elderly subjects and is more common in those with ARG, supporting some previous studies linking pathological TDP-43 deposition with ARG and other pathological tau protein deposits.
近年来，由于 TAR DNA 结合蛋白 43（TDP-43）与肌萎缩性侧索硬化症（ALS）和额颞叶变性有关，因此对其进行了大量研究。几项研究还试图调查 TDP-43 在其他神经退行性疾病（如阿尔茨海默病和帕金森病）中的沉积频率，但很少有研究关注认知正常老年人脑组织中异常 TDP-43 沉积的患病率、分布和组织病理学相关性。我们使用磷酸化 TDP-43 的免疫组织化学方法，对 110 例前瞻性随访和尸检认知正常的受试者（年龄范围 71-100 岁）的内侧颞叶厚、游离冠状切片进行筛选。我们发现病理性 TDP-43 的患病率为 36.4%，主要表现为神经突，而胞质神经元包涵体少见，核内包涵体罕见。关于在老年人中常见的其他伴随病理学，TDP-43 病例具有更高的嗜银颗粒（ARG）（40%对 18.6%）和总体 ARG 密度（中度对稀疏）的患病率。与其他伴随病理学无其他额外关联，包括脑白质稀疏、偶然Lewy 体、神经纤维缠结或淀粉样斑块。这些结果表明 TDP-43 在大量认知正常的老年受试者中沉积，并且在 ARG 患者中更为常见，这支持了一些先前的研究，即病理性 TDP-43 沉积与 ARG 和其他病理性 tau 蛋白沉积有关。
