Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.
Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.
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关岛帕金森痴呆症和阿尔茨海默病的神经原纤维缠结的淀粉样蛋白具有相同的氨基酸序列。
DOI：
10.1073/pnas.84.7.2073
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发表时间：
1987
影响因子：
11.1
通讯作者：
D. Gajdusek
中科院分区：
文献类型：
--
作者：
D. Guiroy;M. Miyazaki;G. Multhaup;P. Fischer;R. Garruto;K. Beyreuther;C. Masters;G. Simms;C. Gibbs;D. Gajdusek
在关岛帕金森-痴呆患者的大脑中存在丰富的神经原纤维缠结（NFT）形式的神经元内淀粉样蛋白，并且没有血管淀粉样蛋白沉积或老年斑形式的神经元外淀粉样蛋白，这使得NFT的纯化不受神经元外淀粉样蛋白的污染。因此，我们已经分离并确定了这些NFT淀粉样原纤维的多肽亚基的氨基酸序列，并描述了它们的超微结构。NFT由单个和成对的螺旋细丝组成，类似于阿尔茨海默病，偶尔也有三重螺旋细丝，由42个氨基酸（A4蛋白）的多肽的多聚体聚集体组成。亚基蛋白的相对分子质量为4.0-4.5 kDa，与阿尔茨海默病和唐氏综合征中NFT的淀粉样蛋白、淀粉样斑块核心和血管淀粉样蛋白沉积物的分子质量相同；在巴拿马帕金森-痴呆的NFT中，淀粉样蛋白原纤维n端15个氨基酸残基的序列与阿尔茨海默病和唐氏综合征的NFT中的淀粉样蛋白、淀粉样斑块核心和脑血管沉积物的序列相同。此外，巴拿马帕金森-痴呆淀粉样蛋白n端多肽长度的异质性或变异与阿尔茨海默病和唐氏综合征相同。我们的观察表明，这些疾病的脑淀粉样蛋白有一个共同的亚基蛋白，这也表明了一个共同的发病机制。
The presence of abundant intraneuronal amyloid in the form of neurofibrillary tangles (NFT) in the brains of Guamanian parkinsonism-dementia patients and the absence of extraneuronal amyloid in the form of vascular amyloid deposits or senile plaques permit the purification of NFT without contamination with extraneuronal amyloid. Thus, we have isolated and determined the amino acid sequence of the polypeptide subunit of the amyloid fibrils of these NFT and describe their ultrastructure. The NFT, which consist of single and paired helical filaments, similar to those of Alzheimer disease, and occasionally triple helical filaments, are composed of multimeric aggregates of a polypeptide of 42 amino acids (A4 protein). The relative molecular mass of the subunit protein, 4.0-4.5 kDa, is the same as the molecular mass of the amyloid of NFT, of the amyloid plaque cores, and of vascular amyloid deposits in Alzheimer disease and Down syndrome; the sequence of 15 amino acid residues at the N-terminus of the amyloid fibrils in the NFT of Guamanian parkinsonism-dementia is identical to that of the amyloid of NFT, amyloid plaque cores, and cerebrovascular deposits in Alzheimer disease and Down syndrome. Furthermore, the heterogeneity, or variation in polypeptide length, of the N-terminus of the amyloid of Guamanian parkinsonism-dementia is the same as in Alzheimer disease and Down syndrome. Our observations indicate that the brain amyloids of these diseases have a common subunit protein, which would also indicate a common pathogenesis.