Biochemical and molecular characterization of neurofibrillary degeneration in frontotemporal dementias
Biochemical and molecular characterization of neurofibrillary degeneration in frontotemporal dementias
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DOI：
10.1159/000051218
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发表时间：
1999-01-01
影响因子：
2.4
通讯作者：
Delacourte, A
中科院分区：
文献类型：
--
作者：
Delacourte, A
神经元变性（NFD）是一种以异常tau蛋白在神经元内聚集为特征的变性过程。这些蛋白质具有疾病特异性的生物化学特征。它们也有一个新皮质的分布，这是典型的疾病。病理性tau蛋白质已被定性和定量分析的所有疾病，可能会出现额颞叶痴呆的临床症状。在阿尔茨海默病中，有时具有额叶优势的疾病，神经元缠结的成对螺旋丝（PHF）由过度磷酸化的tau组成，称为PHF-tau。它们的电泳图谱由四个主要条带（tau 55，64，69，74 kD）组成，这是由于存在六种tau亚型。在皮克病中，来自皮克体的磷酸化tau由两种主要组分（tau 55，64 kD）和次要69 kD组成，所述次要69 kD由缺乏具有翻译的外显子10（E10-）的tau同种型产生。皮质基底节变性（CBD）也具有不同的tau变体模式，具有tau 64、69组分和较小的tau 74。聚集在CBD（和进行性核上性麻痹）中的病理性tau蛋白仅由E10+ tau同种型组成。在额颞叶痴呆非阿尔茨海默病，非皮克（隆德和曼彻斯特标准），我们没有观察到病理性tau蛋白的存在下，在2例，但第三个提出了一个特定的模式的tau，可溶性病理性tau在额颞区。这些数据表明，这一群体可能是异质的。总之，tau蛋白的生化特征区分了四类额颞叶痴呆。观察到的特征性tau表型与每种疾病中受影响的特定神经元网络有关。
Neurofibrillary degeneration (NFD) is a degenerating process characterized by the intraneuronal aggregation of abnormal tau proteins. These proteins have a biochemical signature which is disease-specific. They also have a neocortical distribution which is typical of the disease. Pathological tau proteins have been analyzed qualitatively and quantitatively in all diseases that may present the clinical symptoms of frontotemporal dementias. In Alzheimer's disease, a disease with sometimes a frontal predominance, paired helical filaments (PHF) of neurofibrillary tangles are made of hyperphosphorylated tau, named PHF-tau. Their electrophoretic profile consists of four main bands (tau 55, 64, 69, 74 kD), resulting from the presence of the six tau isoforms. In Pick's disease the phosphorylated tau from Pick bodies are made of two major components (tau 55, 64 kD) and a minor 69 kD resulting from the lack of tau isoforms with the translated exon 10 (E10-). Corticobasal degeneration (CBD) also has a different pattern of tau variants, with tau 64, 69 components and a minor tau 74. Pathological tau proteins that aggregate in CBD (and progressive supranuclear palsy) are exclusively made of E10+ tau isoforms. In frontotemporal dementias non-Alzheimer, non-Pick (Lund and Manchester criteria), we did not observe the presence of pathological tau proteins in 2 cases, but a third one presented a particular pattern of tau, with soluble pathological tau in frontotemporal areas. These data show that this group could be heterogeneous. In conclusion, the biochemical signature of tau distinguishes four classes of frontotemporal dementia. The characteristic tau phenotypes observed are linked to the specific neuronal networks that are affected in each disease.