病理性TDP⁃43蛋白在常见神经系统变性疾病患者杏仁核中的表达变化

Observation on pathological TDP⁃43 in amygdala of patients with common neurodegenerative diseases

目的总结病理性TDP⁃43蛋白在常见神经系统变性疾病中的检出率、形态特征及沉积程度,并探讨其病理学意义。方法回顾收集1994年1月至2019年9月在解放军总医院第二医学中心住院治疗并行尸检的15例病例的脑组织标本,包括5例阿尔茨海默病、3例帕金森病、2例进行性核上性麻痹和5例正常脑老化,行HE染色、卢卡斯快蓝染色、Gallyas银染,以及磷酸化TDP⁃43抗体、β⁃淀粉样蛋白抗体、AT8抗体、α⁃突触核蛋白抗体免疫组化染色,光学显微镜下观察病理性TDP⁃43蛋白病理学特征,并采用半定量法对病理性TDP⁃43蛋白沉积进行分级。结果磷酸化TDP⁃43抗体染色阳性见于5/15例老年脑组织杏仁核,包括2例阿尔茨海默病、1例帕金森病、2例正常脑老化。其中,2/5例阿尔茨海默病杏仁核可见以神经元胞质包涵体为主的重度病理性TDP⁃43蛋白沉积和轻度短神经营养不良线丝;1/3例帕金森病杏仁核罕见神经元胞质包涵体和短神经营养不良线丝;2/5例正常脑老化杏仁核可见罕见或轻度神经元胞质包涵体和短神经营养不良线丝;而2例进行性核上性麻痹杏仁核磷酸化TDP⁃43抗体染色呈阴性;15例均未见杏仁核长神经营养不良线丝,帕金森病、进行性核上性麻痹和正常脑老化均未见胶质细胞胞质包涵体和神经元核内包涵体。结论病理性TDP⁃43蛋白在阿尔茨海默病杏仁核的沉积程度最严重,可加速阿尔茨海默病认知功能下降或降低认知功能障碍阈值。

Objective To observe the detection rate,morphological characteristics and deposition degree of pathological trans⁃activation response DNA binding protein 43(TDP⁃43)in several common neurodegenerative diseases,and to explore its pathological significance.Methods A total of 15 cases with a history of hospitalization in the Second Medical Center,Chinese PLA General Hospital from January 1994 to September 2019 were retrospectively collected,including 5 cases of Alzheimer's disease(AD),3 cases of Parkinson's disease(PD),2 cases of progressive supranuclear palsy(PSP),and 5 cases of normal aging brain.HE staining,Lucas fast blue(LFB)staining,Gallyas⁃Braak silver staining,and immunohistochemical staining ofβ⁃amyloid(Aβ),AT8,phosphorylated TDP⁃43 andα⁃synuclein(α⁃Syn)were performed for amygdala tissue sections.The pathological morphological characteristics of pathological TDP⁃43 protein was observed under a light microscope,and the pathological TDP⁃43 protein was graded by semi⁃quantitative method.Results Phosphorylated TDP⁃43 antibody staining was found in 5/15 of aging brain amygdala tissue,including 2 cases of AD,one case of PD,and 2 cases of normal aging brain.Among them,severe pathological TDP⁃43 protein deposition and mild short neurodystrophy filaments were found in the amygdala of 2/5 cases of AD,mainly neuronal cytoplasmic inclusion bodies.Cytoplasmic inclusions and short neurodystrophy filaments in rare neurons of amygdala in 1/3 cases of PD.Rare or mild neuronal cytoplasmic inclusions and rare short neurodystrophy filaments were found in the amygdala of 2/5 normal aging brain.Two cases of PSP showed negative staining for phosphorylated TDP⁃43 antibody in amygdala.No long amygdala neurodystrophy filaments were found in the 15 patients.No glial cytoplasmic inclusions and neuronal intranuclear inclusions were found in PD,PSP and normal aging brain.Conclusions Pathological TDP⁃43 protein is most severe in the amygdala of AD and may accelerate cognitive decline in AD or lower the threshold of cognitive dysfunction.