Guiroy D C, Mellini M, Miyazaki M, Hilbich C, Safar J, Garruto R M, Yanagihara R, Beyreuther K, Gajdusek D C
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Acta Neuropathol. 1993;86(3):265-74. doi: 10.1007/BF00304141.
Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43-amino acid synthetic peptide homologous to amyloid beta/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian ALS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5-20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4- to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid beta/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid beta/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Guamanians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging.
神经原纤维缠结（NFT）是阿尔茨海默病、唐氏综合征和正常衰老的神经退行性特征之一，在关岛肌萎缩侧索硬化症（ALS）、帕金森痴呆症（PD）以及死于ALS和PD以外原因的神经功能正常的关岛人中，是一种持续且广泛存在的神经病理学表现。关岛ALS和PD患者脑组织切片中的NFT对针对与阿尔茨海默病相关的淀粉样β/A4蛋白同源的43个氨基酸合成肽的抗体（抗SP43）具有免疫反应性。从关岛ALS和PD患者的冷冻脑组织以及神经功能正常的关岛人的组织中提取的NFT具有嗜刚果红性和双折射性。通过负染电子显微镜观察，关岛ALS患者的NFT制剂包含束状和/或孤立的单根、直的、不成对的细丝，神经功能正常的关岛人偶尔有细丝配对，直径为5 - 20纳米。对NFT制剂进行甲酸消化，随后进行十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和尺寸排阻高压液相色谱分析，显示出一种表观分子量为4至4.5 kDa的蛋白质，通过蛋白质印迹分析，该蛋白质对抗SP43具有免疫反应性。用抗SP43对纯化的NFT或SP43进行免疫吸附可消除免疫染色。我们的研究证实了先前的数据，即淀粉样β/A4蛋白存在于关岛PD的NFT中。此外，我们的数据表明，淀粉样β/A4蛋白存在于关岛ALS患者和神经功能正常的关岛人的脑组织NFT中，这表明在阿尔茨海默病和正常脑衰老中，淀粉样蛋白生成与NFT形成具有共同机制。
