Delacourte A
Unité INSERM 156, Lille, France.
Biomed Pharmacother. 1994;48(7):287-95. doi: 10.1016/0753-3322(94)90174-0.
Paired Helical Filaments (PHF) accumulate in the degenerating neurons from the associative cortical brain areas during Alzheimer's disease. They are composed of a triplet of hyperphosphorylated microtubule-associated protein Tau, called Tau 55, 64, 69 or PHF-Tau. The distribution of PHF-Tau in the different brain areas corroborates neuropathological observations and specifies that: the entorhinal cortex and hippocampus are vulnerable regions specifically affected by Alzheimer-type neurofibrillary degeneration during aging, the temporal cortex is already affected at the very first stage of clinical manifestations, almost the whole brain is concerned by neurofibrillary degeneration at the end-stages of the disease. Tau-PHF are also observed in the cortical areas from Parkinson patients with dementia, and more especially in the prefrontal cortex. Tau pathology for Progressive Supranuclear Palsy is significantly different, with a doublet of pathological Tau, namely Tau 64 and 69, in almost all cortical and subcortical areas. Therefore, the presence of pathological Tau proteins in several associative cortical areas is always associated with severe intellectual impairment. Finally, PHF-Tau are powerful biochemical markers of the degenerating process which could be used for setting up an early biological diagnosis test of Alzheimer's disease based upon the immunodetection of PHF antigens in the CSF, as well as for developing experimental models of neurodegeneration.
成对螺旋丝（PHF）在阿尔茨海默病期间在联合皮质脑区的退化神经元中积累。它们由一种高度磷酸化的微管相关蛋白Tau的三联体组成，称为Tau 55、64、69或PHF-Tau。PHF-Tau在不同脑区的分布证实了神经病理学观察结果，并具体表明：内嗅皮质和海马体是衰老过程中特别受阿尔茨海默型神经原纤维变性影响的易损区域，颞叶皮质在临床表现的最初阶段就已受到影响，在疾病末期几乎整个大脑都受到神经原纤维变性的影响。在患有痴呆症的帕金森病患者的皮质区域也观察到了Tau-PHF，尤其是在额叶前部皮质。进行性核上性麻痹的Tau病理学明显不同，在几乎所有皮质和皮质下区域都有病理Tau的二联体，即Tau 64和69。因此，几个联合皮质区域中病理性Tau蛋白的存在总是与严重的智力损害相关。最后，PHF-Tau是退化过程的强大生化标志物，可用于基于脑脊液中PHF抗原的免疫检测建立阿尔茨海默病的早期生物学诊断测试，以及用于开发神经变性的实验模型。
