Mufson Elliott J, Perez Sylvia E, Nadeem Muhammad, Mahady Laura, Kanaan Nicholas M, Abrahamson Eric E, Ikonomovic Milos D, Crawford Fiona, Alvarez Victor, Stein Thor, McKee Ann C
a Department of Neurobiology , Barrow Neurological Institute , Phoenix , AZ , USA.
b Department of Translational Science and Molecular Medicine, College of Human Medicine , Michigan State University , Grand Rapids , MI , USA.
Brain Inj. 2016;30(12):1399-1413. doi: 10.1080/02699052.2016.1219058.
To test the hypothesis that the nucleus basalis of Meynert (nbM), a cholinergic basal forebrain (CBF) cortical projection system, develops neurofibrillary tangles (NFTs) during the progressive pathological stages of chronic traumatic encephalopathy (CTE) in the brain of athletes.
To characterize NFT pathology, tau-antibodies marking early, intermediate and late stages of NFT development in CBF tissue obtained at autopsy from eighteen former athletes and veterans with a history of repetitive mild traumatic brain injury (TBI) were used.
Analysis revealed that cholinergic nbM neurons develop intracellular tau-immunoreactive changes progressively across the pathological stages of CTE. In particular, there was an increase in pre-tangle (phosphorylated pS422) and oligomeric (TOC1 and TNT1) forms of tau in stage IV compared to stage II CTE cases. The nbM neurons also displayed pathologic TDP-43 inclusions and diffuse extracellular and vascular amyloid-β (Aβ) deposits in CTE. A higher percentage of pS422/p75, pS422 and TNT1 labelled neurons were significantly correlated with age at symptom onset, interval between symptom onset and death and age at death.
The development of NFTs within the cholinergic nbM neurons could contribute to an axonal disconnection in CTE. Further studies are needed to determine the mechanism driving NFT formation in the nbM neurons and its relation to chronic cognitive dysfunction in CTE.
验证如下假说，即Meynert基底核（nbM），一种胆碱能基底前脑（CBF）皮质投射系统，在运动员大脑慢性创伤性脑病（CTE）的进行性病理阶段会形成神经原纤维缠结（NFTs）。
为了描述NFT病理学特征，使用了tau抗体，这些抗体可标记从18名有重复性轻度创伤性脑损伤（TBI）病史的前运动员和退伍军人尸检获得的CBF组织中NFT发展的早期、中期和晚期阶段。
分析显示，胆碱能nbM神经元在CTE的病理阶段中逐渐出现细胞内tau免疫反应性变化。特别是，与CTE II期病例相比，IV期tau的缠结前（磷酸化pS422）和寡聚体（TOC1和TNT1）形式有所增加。nbM神经元在CTE中还显示出病理性TDP - 43包涵体以及弥漫性细胞外和血管淀粉样β（Aβ）沉积。较高比例的pS422/p75、pS422和TNT1标记神经元与症状发作时的年龄、症状发作与死亡之间的间隔以及死亡时的年龄显著相关。
胆碱能nbM神经元内NFT的形成可能导致CTE中的轴突断开。需要进一步研究以确定驱动nbM神经元中NFT形成的机制及其与CTE中慢性认知功能障碍的关系。
