Castellani Rudy J, Perry George, Iverson Grant L
From the Division of Neuropathology, University of Maryland School of Medicine, Baltimore, Maryland (RJC); College of Sciences, University of Texas, San Antonio, San Antonio, Texas (GP); and Department of Physical Medicine and Rehabilitation, Harvard Medical School; Spaulding Rehabilitation Hospital; MassGeneral Hospital for Children Sports Concussion Program; and Red Sox Foundation and Massachusetts General Hospital Home Base Program, Boston, Massachusetts (GLI).
J Neuropathol Exp Neurol. 2015 Jun;74(6):493-9. doi: 10.1097/NEN.0000000000000193.
Accumulation of phosphorylated tau (p-tau) is accepted by many as a long-term consequence of repetitive mild neurotrauma based largely on brain findings in boxers (dementia pugilistica) and, more recently, former professional athletes, military service members, and others exposed to repetitive head trauma. The pathogenic construct is also largely accepted and suggests that repetitive head trauma (typically concussions or subconcussive forces) acts on brain parenchyma to produce a deleterious neuroinflammatory cascade, encompassing p-tau templating, transsynaptic neurotoxicity, progressive neurodegenerative disease, and associated clinical features. Some caution before accepting these concepts and assumptions is warranted, however. The association between the history of concussion and findings of p-tau at autopsy is unclear. Concussions and subconcussive head trauma exposure are poorly defined in available cases, and the clinical features reported in chronic traumatic encephalopathy are not at present distinguishable from other disorders. Because control groups are limited, the idea that p-tau drives the disease process via protein templating or some other mechanism is preliminary. Much additional research in chronic traumatic encephalopathy is needed to determine if it has unique neuropathology and clinical features, the extent to which the neuropathologic alterations cause the clinical features, and whether it can be identified accurately in a living person.
磷酸化tau蛋白（p-tau）的积累被许多人认为是重复性轻度神经创伤的长期后果，这主要基于对拳击手（拳击员痴呆症）以及最近对前职业运动员、军人和其他遭受重复性头部创伤者的脑部研究结果。这种致病机制也在很大程度上被认可，它表明重复性头部创伤（通常是脑震荡或亚脑震荡力）作用于脑实质，引发有害的神经炎症级联反应，包括p-tau模板化、跨突触神经毒性、进行性神经退行性疾病以及相关临床特征。然而，在接受这些概念和假设之前，需要谨慎对待。脑震荡病史与尸检时p-tau的发现之间的关联尚不清楚。在现有病例中，脑震荡和亚脑震荡头部创伤暴露的定义不明确，而且目前慢性创伤性脑病所报告的临床特征与其他疾病无法区分。由于对照组有限，认为p-tau通过蛋白质模板化或其他机制驱动疾病进程的观点尚属初步。需要对慢性创伤性脑病进行更多的研究，以确定它是否具有独特的神经病理学和临床特征、神经病理学改变导致临床特征的程度，以及是否能够在活体中准确识别。
