Life-long overexpression of S100β in Down's syndrome:: Implications for Alzheimer pathogenesis
Life-long overexpression of S100β in Down's syndrome:: Implications for Alzheimer pathogenesis
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DOI：
10.1016/s0197-4580(98)00074-8
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发表时间：
1998-09-01
影响因子：
4.2
通讯作者：
Mrak, RE
中科院分区：
文献类型：
--
作者：
Griffin, WST;Sheng, JG;Mrak, RE
神经突生长促进因子S100 β的慢性过度表达与阿尔茨海默病神经炎斑块的发病机制有关。这种斑块在中年唐氏综合症中几乎是普遍存在的，使唐氏症成为阿尔茨海默病的自然模型。我们确定了过度表达S100 β的星形胶质细胞和过度表达β-淀粉样前体蛋白（β-APP）的神经元的数量，并测定了20名唐氏综合征患者（妊娠17周至68岁）新皮质中的神经元缠结。与对照组相比，在所有年龄段的唐氏患者中，S100 β免疫反应性（S100 β（+））星形胶质细胞的数量是对照组的两倍：胎儿，年轻人和成人（每个年龄组的p = 0.01或更好）。它们被激活（即，扩大），和强烈的免疫反应，即使在胎儿组。胎儿和青年唐氏症患者无神经系统改变。年轻和成年唐氏病患者中S100 β（+）星形胶质细胞的数量与过表达β-APP的神经元的数量相关（p < 0.05）。我们的研究结果与以下观点一致，即促进S100 β慢性过度表达的条件（包括唐氏综合征）可能会增加日后患阿尔茨海默病的风险。(C)1998年爱思唯尔科学公司
Chronic overexpression of the neurite growth-promoting factor S100 beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100 beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100 beta-immunoreactive (S100 beta(+)) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100 beta(+) astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions-including Down's syndrome-that promote chronic overexpression of S100 beta may confer increased risk for later development of Alzheimer's disease. (C) 1998 Elsevier Science Inc.