Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies

Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies
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DOI:
10.1016/j.neulet.2004.01.060
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发表时间:
2004-04-15
影响因子:
2.5
通讯作者:
Hasegawa, M
Hasegawa, M
中科院分区:
医学4区
文献类型:
--
作者:
Umeda, Y;Taniguchi, S;Hasegawa, M

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tau mRNA剪接异常导致与17号染色体相关的额颞叶痴呆和帕金森病,并且在散发性tau病变如进行性核上性麻痹(PSP)或皮质基底变性(CBD)中也存在类似的改变。我们分析了三重复(3R)和四重复(4R) tau亚型在家族性和散发性tau病患者大脑中的表达。通过RT-PCR分析,不仅在进展性核上性麻痹或皮质基底变性严重患者中,而且在阿尔茨海默病或皮克病患者中也检测到3R tau mRNA水平的降低。3R tau转录本的水平与神经丝转录本的水平密切相关。相比之下,胶质原纤维酸性蛋白和髓鞘碱性蛋白在所有脑中的表达相似。这些结果表明,在散发性tau病中,与神经元元素缺失相关的3R tau mRNA的减少可能在很大程度上促进了4R/3R tau mRNA比值的增加。2004爱思唯尔爱尔兰有限公司版权所有。
Abnormalities in tau mRNA splicing cause frontotemporal dementia and parkinsonism linked to chromosome 17, and similar alterations are suggested in sporadic tauopathies such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). We have analyzed the expression of three-repeat (3R) and four-repeat (4R) tau isoforms in brains with familial and sporadic tauopathies. By RT-PCR analysis, decreased levels of 3R tau mRNA were detected not only in severely affected cases with progressive supranuclear palsy or corticobasal degeneration but also in cases with Alzheimer's disease or Pick's disease. Levels of 3R tau transcripts were closely correlated with levels of neurofilament transcripts. By contrast, expressions of glial fibrillary acidic protein and myelin basic protein were similar in all brains. These results suggest that decrease of 3R tau mRNA associated with loss of neuronal element may largely contribute to the increased ratio of 4R/3R tau mRNA in sporadic tauopathies. (C) 2004 Elsevier Ireland Ltd. All rights reserved.