Kallikrein-related peptidase 6 in Alzheimer's disease and vascular dementia
Kallikrein-related peptidase 6 in Alzheimer's disease and vascular dementia
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DOI：
10.1016/j.brainres.2010.09.017
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发表时间：
2010-12-06
期刊：
影响因子：
2.9
通讯作者：
Love, Seth
中科院分区：
文献类型：
--
作者：
Ashby, Emma L.;Kehoe, Patrick G.;Love, Seth
人类钾化肽相关肽酶6 （KLK6）在中枢神经系统中高度表达，尽管这种丝氨酸蛋白酶的生理作用尚不清楚，但体外底物包括淀粉样前体蛋白和细胞外基质成分，它们在神经系统疾病，特别是阿尔茨海默病（AD）中发生改变。我们采用免疫组化方法研究了KLK6在颞叶皮层和白质中的分布。并测量了15例AD、15例VaD和15例对照脑的额叶和颞叶皮层中KLK6 mRNA和蛋白水平，免疫组织化学显示KLK6仅限于内皮细胞。通过测量因子VIII相关抗原调整血管密度变化后，我们发现，AD患者的额叶皮层中KLK6蛋白和mRNA水平显著降低，而颞叶皮层中KLK6蛋白和mRNA水平则显著降低。我们的研究结果表明，KLK6表达的改变可能导致AD和VaD的血管异常(C) 2010 Elsevier B V All rights reserved
Human kallikrein related peptidase 6 (KLK6) is highly expressed in the central nervous system Although the physiological roles of this serine protease are unknown, in vitro substrates include amyloid precursor protein and components of the extracellular matrix, which are altered in neurological disease, particularly Alzheimer's disease (AD) We have compared KLK6 expression in post mortem brain tissue in AD, vascular dementia (VaD) and controls We studied the distribution of KLK6 in the temporal cortex and white matter by immunohistochemistry, and measured KLK6 mRNA and protein levels in the frontal and temporal cortex from 15 AD 15 VaD and 15 control brains Immunohistochemistry showed KLK6 to be restricted to endothelial cells After adjustment for variations in vessel density by measurement of factor VIII related antigen we found KLK6 protein and mRNA levels to be significantly decreased in the frontal but not the temporal cortex in AD In VaD, KLK6 protein level was significantly increased in the frontal cortex Our findings suggest that an altered KLK6 expression may contribute to vascular abnormalities in AD and VaD (C) 2010 Elsevier B V All rights reserved