Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy

Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.

原发性衰老相关性tau病在中国人群中的临床病理学研究

目的:分析中国人群中原发性衰老相关性tau病(PART)的临床病理学特点,并比较其与老年性痴呆之间的差异。创新点:PART为新近提出的概念,其与老年性痴呆的关系尚存在争论。目前未见针对中国人群PART的相关报道。本文首次报道了浙江大学医学院中国人脑库中的PART的临床病理学特点。方法:回顾性分析相关病例,严格纳入标准。PART在中国人群中常见,50岁以上人群占47%。平均年龄(76±12)岁,女性14例(30%),男性32例(70%)。免疫组织化学法显示,按磷酸化tau的Braak分期,PART大多为I到Ш期。异常蛋白TDP43和p62在PART中高表达,分别为67%和70%;在老年性痴呆中分别为83%和83%。TDP43和p62共表达在PART为55%,在老年性痴呆为79%。其中海马为PART常见累及部位,TDP43为61%,p62为63%。仅4%的PART患者表现为轻度认知障碍。结论:PART在中国人群中常见;PART大多无明显痴呆症状;异常蛋白TDP43和p62在PART中高表达,与老年性痴呆相比存在差异。