Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments.
Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments.
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DOI：
10.1073/pnas.94.8.4113
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发表时间：
1997-04
影响因子：
11.1
通讯作者：
M. Spillantini;M. Goedert;R. Crowther;J. Murrell;M. Farlow;B. Ghetti
中科院分区：
文献类型：
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作者：
M. Spillantini;M. Goedert;R. Crowther;J. Murrell;M. Farlow;B. Ghetti
由过度磷酸化的微管相关蛋白tau形成的神经纤维病变不仅是阿尔茨海默病的典型神经病理特征之一，而且在许多其他神经退行性疾病中也存在。在这里，我们描述了一种新的常染色体显性遗传病，称为家族性“多系统痴呆伴老年前期痴呆”，其特征是神经元和神经胶质细胞中都有大量的tau蛋白纤维沉积。没有可检测到的β-淀粉样蛋白沉积。Tau沉淀物的形式是扭曲的细丝，其直径和周期与阿尔茨海默病的成对螺旋细丝不同。它们被磷酸化非依赖性和依赖性的抗tau抗体染色。此外，在受累的神经和神经胶质细胞中，tau免疫反应与硫酸肝素共存。从家族性多系统痴呆伴老年期痴呆患者的微丝中提取的tau蛋白显示一条较小的72 kDa条带，以及和68 kDa两条主要条带，其中主要含有过度磷酸化的4个重复序列tau亚型的383和412个氨基酸。
Neurofibrillary lesions made of hyperphosphorylated microtubule-associated protein tau constitute not only one of the defining neuropathological features of Alzheimer disease but also are present in a number of other neurodegenerative diseases with dementia. Here we describe a novel autosomal dominant disease named familial "multiple system tauopathy with presenile dementia," which is characterized by abundant fibrillary deposits of tau protein in both neurons and glial cells. There are no detectable deposits of beta-amyloid. The tau deposits are in the form of twisted filaments that differ in diameter and periodicity from the paired helical filaments of Alzheimer disease. They are stained by both phosphorylation-independent and -dependent anti-tau antibodies. Moreover, tau immunoreactivity coexists with heparan sulfate in affected nerve and glial cells. Tau protein extracted from filaments of familial multiple system tauopathy with presenile dementia shows a minor 72-kDa band and two major bands of 64 and 68 kDa that contain mainly hyperphosphorylated four-repeat tau isoforms of 383 and 412 amino acids.