Wostyn Peter, Audenaert Kurt, De Deyn Peter Paul
Department of Psychiatry, PC Sint-Amandus, Reigerlostraat 10, 8730 Beernem, Belgium.
Clin Neurol Neurosurg. 2008 Feb;110(2):101-9. doi: 10.1016/j.clineuro.2007.10.011. Epub 2007 Dec 3.
In this review, we focus on the coexistence of Alzheimer's disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. In considering possible mechanisms underlying Alzheimer-type changes in these diseases, we briefly summarize recent evidence indicating that caspase activation and abnormal processing of beta-amyloid precursor protein, which are important events in Alzheimer's disease, may play a role both in glaucoma and following traumatic brain injury. With regard to normal pressure hydrocephalus, evidence suggests that changes in cerebrospinal fluid circulatory dynamics ultimately may result in reduced clearance of neurotoxins, such as beta-amyloid peptides and tau protein, that play a role in the pathogenesis of Alzheimer's disease. Data presented in this review could be interpreted to suggest that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to increased levels of mechanical stress. Evidence for such a relationship is of major importance because it may support an association between elevated mechanical load and the development of Alzheimer-type lesions. Further studies are warranted, however, especially to elucidate the role of elevated mechanical forces in Alzheimer's disease neuropathogenesis.
在本综述中，我们关注阿尔茨海默病相关变化在诸如正常压力脑积水和创伤性脑损伤等脑部疾病以及视网膜神经节细胞水平的青光眼中的共存情况。这是一组影响中枢神经系统组织的疾病，其特征为颅内或眼内压升高和/或局部剪切应力及应变增加。在考虑这些疾病中阿尔茨海默型变化的潜在机制时，我们简要总结了近期证据，这些证据表明，半胱天冬酶激活和β-淀粉样前体蛋白的异常加工，这些在阿尔茨海默病中是重要事件，可能在青光眼和创伤性脑损伤后都发挥作用。关于正常压力脑积水，有证据表明脑脊液循环动力学的变化最终可能导致神经毒素清除减少，如在阿尔茨海默病发病机制中起作用的β-淀粉样肽和tau蛋白。本综述中呈现的数据可以解释为表明这些疾病中的阿尔茨海默型变化可能至少部分是由于中枢神经系统组织暴露于增加的机械应力水平所致。这种关系的证据至关重要，因为它可能支持机械负荷升高与阿尔茨海默型病变发展之间的关联。然而，仍需要进一步研究，特别是要阐明升高的机械力在阿尔茨海默病神经发病机制中的作用。
