Mrak Robert E, Griffin W Sue T
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
J Neuropathol Exp Neurol. 2007 Aug;66(8):683-6. doi: 10.1097/nen.0b013e31812503e1.
Cortical Lewy body disease as a cause of dementia has been recognized for more than 40 years. Only in the past 15 to 20 years, however, has the true frequency of this entity come to be appreciated, primarily because of the advent of sensitive and specific immunohistochemical diagnostic techniques. We now know that there is frequent and extensive overlap, both clinically and pathologically, between Lewy body and Alzheimer diseases. Although some of this overlap may be attributable to common genetic and environmental risk factors, it is also now apparent that the 2 diseases share common neuroinflammatory mechanisms involving activation of microglia, overexpression of interleukin-1 and other inflammatory mediators, and inflammatory toxicity to neurons. Activated microglia are found in association with alpha-synuclein-containing neurons and glia in Parkinson disease, in dementia with Lewy bodies, and in multiple system atrophy, and these associations are reminiscent of microglial associations with neurofibrillary tangle-containing neurons in Alzheimer disease. In vitro and in vivo experimental work has shown reciprocal induction between alpha-synuclein and injured neurons on one hand and activated microglia and cytokine overexpression on the other. These neuroinflammatory processes may be a common link driving progression in both diseases and explaining the frequent overlap between the 2 diseases.
皮质路易体病作为痴呆的一种病因已被认识40多年了。然而，仅在过去15到20年里，人们才开始认识到这种疾病的实际发病率，这主要归功于敏感且特异的免疫组化诊断技术的出现。我们现在知道，路易体病和阿尔茨海默病在临床和病理上都经常存在广泛重叠。尽管这种重叠部分可能归因于共同的遗传和环境危险因素，但现在也很明显，这两种疾病具有共同的神经炎症机制，包括小胶质细胞激活、白细胞介素-1和其他炎症介质的过度表达以及对神经元的炎症毒性。在帕金森病、路易体痴呆和多系统萎缩中，活化的小胶质细胞与含有α-突触核蛋白的神经元和神经胶质相关联，这些关联让人联想到阿尔茨海默病中与含有神经原纤维缠结的神经元相关联的小胶质细胞。体外和体内实验研究表明，一方面α-突触核蛋白与受损神经元之间相互诱导，另一方面活化的小胶质细胞与细胞因子过度表达之间相互诱导。这些神经炎症过程可能是推动这两种疾病进展的共同环节，并解释了这两种疾病之间频繁的重叠现象。
