Evidence that aging and amyloid promote microglial cell senescence
Evidence that aging and amyloid promote microglial cell senescence
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DOI：
10.1089/rej.2006.9096
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发表时间：
2007-03-01
影响因子：
2.6
通讯作者：
Streit, Wolfgang J.
中科院分区：
文献类型：
--
作者：
Flanary, Barry E.;Sammons, Nicole W.;Streit, Wolfgang J.
已知高龄和脑内淀粉样蛋白沉积的存在是阿尔茨海默病（AD）中神经变性发展的主要风险因素，并且两者都与小胶质细胞活化相关。然而，激活的小胶质细胞在AD发病机制中的具体作用仍然没有得到解决。在这里，我们报告说，小胶质细胞表现出显着的端粒缩短和端粒酶活性降低与正常老化的大鼠，在人类中有一个倾向端粒缩短与存在痴呆症。含有高淀粉样蛋白负荷的人脑表现出比非痴呆、无淀粉样蛋白对照受试者显著更高程度的小胶质细胞营养不良。总的来说，这些发现表明，与端粒缩短和正常衰老相关的小胶质细胞衰老因淀粉样蛋白的存在而加剧。提示小胶质细胞变性是AD发病机制中的一个因素。
Advanced age and presence of intracerebral amyloid deposits are known to be major risk factors for development of neurodegeneration in Alzheimer's disease (AD), and both have been associated with microglial activation. However, the specific role of activated microglia in AD pathogenesis remains unresolved. Here we report that microglial cells exhibit significant telomere shortening and reduction of telomerase activity with normal aging in rats, and that in humans there is a tendency toward telomere shortening with presence of dementia. Human brains containing high amyloid loads demonstrate a significantly higher degree of microglial dystrophy than nondemented, amyloid-free control subjects. Collectively, these findings show that microglial cell senescence associated with telomere shortening and normal aging is exacerbated by the presence of amyloid. They suggest that degeneration of microglia is a factor in the pathogenesis of AD.