In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury
In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury
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DOI：
10.1126/scitranslmed.aaw1993
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发表时间：
2019-09-04
影响因子：
17.1
通讯作者：
Sharp, David J.
中科院分区：
文献类型：
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作者：
Gorgoraptis, Nikos;Li, Lucia M.;Sharp, David J.
创伤性脑损伤（TBI）可引发进行性神经变性，在单次中重度TBI后数年观察到tau病理学。在体内识别这种类型的创伤后病理学可能有助于理解tau病理学在TBI病理生理学中的作用。我们使用flortaucipir正电子发射断层扫描（PET）来研究人类单次TBI多年后是否存在tau病理。我们检查了PET数据与脑脊液（CSF）中神经变性标志物、结构磁共振成像测量和认知能力的关系。大脑flortaucipir结合是可变的，许多TBI参与者显示皮质和白色物质区域增加。在组水平上，与健康对照组相比，TBI中右枕叶皮质中的flortaucipir结合增加。Flortaucipir结合与TBI中总tau、磷酸化tau和泛素羧基末端水解酶L1 CSF浓度增加以及各向异性分数和白色组织密度降低相关。载脂蛋白E（APOE）β 4基因型影响flortaucipir结合与损伤后时间、CSF β淀粉样蛋白1-42（A β 42）浓度、白色组织密度和TBI纵向简易精神状态检查评分之间的关系。结果表明，tau PET是研究TBI后与tau病变相关的进行性神经变性的一种有前途的方法。
Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) epsilon 4 genotype affected the relationship between flortaucipir binding and time since injury, CSF beta amyloid 1-42 (A beta 42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.