Brain Injury and Repair, Departmentof Neurosurgery, University of Pennsylvania School of Medicine, 3320 Smith Walk, Hayden Hall 105, Philadelphia, Pennsylvania 19104, USA; University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Nat Rev Neurosci. 2010 May;11(5):361-70. doi: 10.1038/nrn2808.
Traumatic brain injury (TBI) has devastating acute effects and in many cases seems to initiate long-term neurodegeneration. Indeed, an epidemiological association between TBI and the development of Alzheimer's disease (AD) later in life has been demonstrated, and it has been shown that amyloid-β (Aβ) plaques — one of the hallmarks of AD — may be found in patients within hours following TBI. Here, we explore the mechanistic underpinnings of the link between TBI and AD, focusing on the hypothesis that rapid Aβ plaque formation may result from the accumulation of amyloid precursor protein in damaged axons and a disturbed balance between Aβ genesis and catabolism following TBI.
创伤性脑损伤(TBI)具有破坏性的急性效应,在许多情况下似乎会引发长期的神经退行性变。事实上,已经证明 TBI 与晚年发生阿尔茨海默病(AD)之间存在流行病学关联,并且已经表明,在 TBI 后数小时内,淀粉样蛋白-β(Aβ)斑块——AD 的标志之一——可能在患者中发现。在这里,我们探讨了 TBI 和 AD 之间联系的机制基础,重点关注以下假设:即快速 Aβ 斑块形成可能是由于损伤轴突中淀粉样前体蛋白的积累以及 TBI 后 Aβ 生成和分解代谢之间平衡的破坏所致。