Crowther R A
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2288-92. doi: 10.1073/pnas.88.6.2288.
The presence of abundant neurofibrillary tangles in certain areas of the brain constitutes one of the defining pathological characteristics of Alzheimer disease. The predominant component of the tangle is an abnormal fibrous assembly known as the paired helical filament (PHF). The PHF is formed by a twisted double-helical ribbon of subunits that gives rise to an image alternating in width between 8 nm and 20 nm with a cross-over spacing of 80 nm. Also found in tangles is the straight filament (SF), a different kind of abnormal filament, about 15 nm wide, that does not exhibit the marked modulation in width shown by the PHF. It is reported herein that PHFs and SFs form hybrid filaments displaying both morphologies, that PHFs and SFs share surface epitopes, and that computed maps reveal a similar C-shaped morphological unit in PHFs and SFs, though differing in relative arrangement in the two types of filament. The observations imply that the SF is a structural variant of the PHF and establish a common unit of assembly for these two pathological filaments.
大脑某些区域存在大量神经原纤维缠结是阿尔茨海默病的主要病理特征之一。缠结的主要成分是一种异常的纤维聚集体，称为双螺旋丝（PHF）。PHF由亚基扭曲的双螺旋带形成，产生宽度在8纳米至20纳米之间交替、交叉间距为80纳米的图像。在缠结中还发现了直丝（SF），这是一种不同类型的异常细丝，宽度约为15纳米，不表现出PHF所显示的明显宽度调制。本文报道，PHF和SF形成了兼具两种形态的混合细丝，PHF和SF共享表面表位，并且计算图谱显示PHF和SF中存在相似的C形形态单元，尽管在两种细丝中的相对排列不同。这些观察结果表明，SF是PHF的结构变体，并为这两种病理细丝建立了共同的组装单元。
