Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?
Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?
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DOI：
10.1016/j.expneurol.2015.06.015
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发表时间：
2016-01
影响因子：
5.3
通讯作者：
Burns MP
中科院分区：
文献类型：
--
作者：
Washington PM;Villapol S;Burns MP
人类创伤性脑损伤（TBI）病例的神经病理学研究已经描述了在单次严重TBI后急性淀粉样蛋白斑块，以及重复轻度TBI（mTBI）后的tau病理学。这有助于推动一种假设，即单一中度至重度TBI增加了发展迟发性阿尔茨海默病（AD）的风险，而mTBI增加了发展慢性创伤性脑病（CTE）的风险。在这篇综述中，我们严格评估这一立场，检查流行病学和病例对照人类研究，神经病理学证据，和临床前研究。流行病学研究强调，TBI与发展多种类型痴呆症的风险增加有关，而不仅仅是AD型痴呆症，并且TBI还可以引发其他神经退行性疾病，如帕金森病。此外，对单次TBI和重复mTBI的人类尸检研究可以显示淀粉样蛋白、tau、TDP-43和路易体病理学的组合，表明TBI的神经病理学最好被描述为“多发性病理学”。临床前研究证实，与神经退行性疾病的发展相关的多种蛋白质在TBI后在大脑中积累。单次TBI和重复mTBI的慢性后遗症具有共同的神经病理学特征和经典定义的神经退行性疾病的临床症状。然而，虽然重复mTBI后发生的慢性认知和神经行为障碍的范围被视为CTE的症状，但单次TBI后发生的慢性认知和神经行为症状的范围被认为代表不同的神经退行性疾病，如AD。这些数据支持的建议，TBI诱导的神经退行性疾病的多种表现一起归类为创伤性脑病或创伤诱导的神经退行性疾病，无论性质或频率的沉淀TBI。
Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer’s disease (AD), while mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position—examining epidemiological and case-control human studies, neuropathological evidence, and preclinical studies. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson’s disease. Further, human post-mortem studies on either single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a ‘polypathology’. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI are viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI.