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阿尔茨海默病中病变及未病变脑区tau信使核糖核酸和可溶性tau亚型的表达

Expression of tau mRNA and soluble tau isoforms in affected and non-affected brain areas in Alzheimer's disease.

作者信息

Boutajangout A, Boom A, Leroy K, Brion J P

机构信息

Laboratory of Histology, Neuropathology and Neuroanatomy, Université Libre de Bruxelles, School of Medicine, 808 route de Lennik, B-1070 Brussels, Belgium.

出版信息

FEBS Lett. 2004 Oct 8;576(1-2):183-9. doi: 10.1016/j.febslet.2004.09.011.

Abstract

In Alzheimer's disease (AD), selective expression of tau isoforms might underlie the susceptibility of different brain areas to develop neurofibrillary tangles and this pattern might change in the disease. In this study, we have analyzed in control subjects and in sporadic AD patients the pattern of expression of tau mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter), moderately affected (occipital striate cortex, thalamus, caudate nucleus, and putamen) or strongly affected by neurofibrillary tangles (temporal and frontal associative cortex). After RT-PCR amplification, five products corresponding to the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon 10 and without exon 10 were identified. In control subjects, these five PCR products were present in all areas except in white matter, where transcripts with exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of transcripts was observed in different areas, regardless of the presence of neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six tau isoforms were identified in the same areas by immunoblotting, including in the white matter, suggesting that most tau isoforms with exons 2 and 3 are transported along axons. The relative expression of 0N3R isoforms was higher in the temporal cortex than in the cerebellar cortex, both in control and AD subjects. The qualitative pattern of expression was identical in subjects with or without an APOE4 allele. Our results suggest that splicing regulation of the tau gene and the relative expression of tau isoforms are not significantly changed in sporadic cases of the disease, although differential expression of tau isoforms in temporal cortex might underlie this brain area susceptibility to neurofibrillary tangles formation.

摘要

在阿尔茨海默病(AD)中,tau异构体的选择性表达可能是不同脑区易发生神经原纤维缠结的基础,且这种模式在疾病过程中可能会发生变化。在本研究中,我们分析了对照受试者和散发性AD患者中,未受影响区域(小脑皮质、白质)、中度受影响区域(枕纹状皮质、丘脑、尾状核和壳核)或受神经原纤维缠结严重影响区域(颞叶和额叶联合皮质)中tau mRNA和tau蛋白的表达模式。经过逆转录聚合酶链反应(RT-PCR)扩增后,鉴定出了五种与包含外显子2和3、外显子2、不含外显子2或3、含外显子10以及不含外显子10的tau mRNA相对应的产物。在对照受试者中,除白质外,所有区域均存在这五种PCR产物,在白质中未鉴定出含有外显子2或外显子2和3的转录本。在AD患者中,无论是否存在神经原纤维病变,不同区域均观察到相同的转录本模式。对可溶性tau蛋白进行去磷酸化处理后,通过免疫印迹在相同区域鉴定出了六种tau异构体,包括在白质中,这表明大多数含有外显子2和3的tau异构体是沿轴突运输的。在对照受试者和AD受试者中,0N3R异构体在颞叶皮质中的相对表达均高于小脑皮质。有无APOE4等位基因的受试者中,表达的定性模式相同。我们的结果表明,在该疾病的散发性病例中,tau基因的剪接调控和tau异构体的相对表达没有显著变化,尽管颞叶皮质中tau异构体的差异表达可能是该脑区易发生神经原纤维缠结形成的基础。

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