Bussière T, Hof P R, Mailliot C, Brown C D, Caillet-Boudin M L, Perl D P, Buée L, Delacourte A
INSERM U 422, Place de Verdun, F-59045 Lille, France.
Acta Neuropathol. 1999 Mar;97(3):221-30. doi: 10.1007/s004010050978.
Neuronal inclusions with bundles of abnormal filaments made of tau polymers are found in numerous diseases with neurofibrillary degeneration. Tau proteins are the basic components of paired helical filaments (PHF) in Alzheimer's disease (AD), and are abnormally phosphorylated. A disease-specific phosphorylation site at serine422 was demonstrated on PHF, but not on tau proteins from biopsy-derived brain samples. In the present study, we report the characterization of a polyclonal antibody (988) against the serine422 phosphorylation site. By using biochemical and immunohistochemical methods, we confirmed that it is not found on tau proteins from biopsy- or autopsy-derived control samples, and we investigated the presence of this epitope on tau proteins in several neurodegenerative disorders, including AD, Down syndrome (DS), Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), postencephalitic parkinsonism (PEP) and Pick's disease (PiD). By Western blotting, antibody 988 labeled the characteristic tau triplet (tau 55, 64, 69) in AD, DS, Guamanian ALS/PDC and PEP. PSP and CBD exhibited their typical tau doublet (tau 64, 69), whereas the doublet tau 55 and 64 was detected in PiD. In all of these neurodegenerative disorders, antibody 988 clearly labeled NFT and dystrophic neurites, as well as Pick bodies in PiD cases, whereas no staining was observed in control cases. These data indicate that phosphorylation of serine422 on tau proteins is a common feature among neurodegenerative disorders and is therefore not specific of AD. Moreover, phosphorylation of this epitope permits the distinction between normal tau proteins and pathological tau proteins.
在许多伴有神经原纤维变性的疾病中，均可发现由tau聚合物构成的异常细丝束所形成的神经元包涵体。tau蛋白是阿尔茨海默病（AD）中双螺旋细丝（PHF）的基本成分，且发生了异常磷酸化。在PHF上证实了丝氨酸422处存在疾病特异性磷酸化位点，但在活检获得的脑样本中的tau蛋白上未发现该位点。在本研究中，我们报告了一种针对丝氨酸422磷酸化位点的多克隆抗体（988）的特性。通过生化和免疫组化方法，我们证实其在活检或尸检获得的对照样本的tau蛋白上未发现，并且我们研究了该表位在几种神经退行性疾病的tau蛋白中的存在情况，这些疾病包括AD、唐氏综合征（DS）、关岛肌萎缩侧索硬化/帕金森痴呆综合征（ALS/PDC）、皮质基底节变性（CBD）、进行性核上性麻痹（PSP）、脑炎后帕金森综合征（PEP）和皮克病（PiD）。通过蛋白质印迹法，抗体988标记了AD、DS、关岛ALS/PDC和PEP中的特征性tau三联体（tau 55、64、69）。PSP和CBD表现出其典型的tau双峰（tau 64、69），而在PiD中检测到双峰tau 55和64。在所有这些神经退行性疾病中，抗体988均清晰地标记了神经原纤维缠结（NFT）和营养不良性神经突，以及PiD病例中的皮克小体，而在对照病例中未观察到染色。这些数据表明，tau蛋白上丝氨酸422的磷酸化是神经退行性疾病中的一个共同特征，因此并非AD所特有。此外，该表位的磷酸化允许区分正常tau蛋白和病理性tau蛋白。
