Spillantini M G, Crowther R A, Goedert M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Acta Neuropathol. 1996 Jul;92(1):42-8. doi: 10.1007/s004010050487.
Alzheimer's disease (AD) is characterised neuropathologically by the presence of abundant extracellular beta-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of presenile dementia with neurofibrillary pathology and no beta-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120-127]. We have compared the tau pathology in this familial form of presenile dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial presenile dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of beta-amyloid deposits and that their presence is associated with dementia.
阿尔茨海默病（AD）的神经病理学特征是存在大量细胞外β-淀粉样蛋白沉积物和细胞内神经原纤维病变，包括神经原纤维缠结、神经毡丝和老年斑神经突，其中含有由高度磷酸化的微管相关蛋白tau构成的双螺旋丝（PHF）。最近描述了一种新的早老性痴呆家族形式，具有神经原纤维病理学特征但无β-淀粉样蛋白沉积物[Sumi等人（1992年），《神经病学》42: 120 - 127]。我们比较了这种早老性痴呆家族形式与AD中的tau病理学。为此，我们使用了电子显微镜、免疫印迹和免疫组织化学方法，采用了依赖磷酸化的（PHF1、AT8、AT100、AT180、AT270、12E8）和不依赖磷酸化的（BR133、BR134）抗tau抗体。我们发现，在这两种疾病中，分散的PHF在结构、生化和免疫方面是相同的；它们被所有使用过的抗tau抗体染色，在免疫印迹中，PHF - tau表现为60、64和68 kDa的三条主要条带。然而，虽然抗tau抗体可染色AD脑中的神经原纤维缠结、神经毡丝和神经突斑，但在家族性早老性痴呆中未发现神经突斑。这些结果表明，在这两种疾病中tau经历相同的修饰；它们证实，像AD中的神经原纤维缠结和神经毡丝可以独立于β-淀粉样蛋白沉积物存在，并且它们的存在与痴呆有关。
