Schwab C, Akiyama H, McGeer E G, McGeer P L
Kinsmen Laboratory of Neurological Research and the Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada.
J Neuropathol Exp Neurol. 1998 Dec;57(12):1131-7. doi: 10.1097/00005072-199812000-00004.
Neurofibrillary tangles (NFTs) form in a number of neurodegenerative disorders. In Alzheimer disease (AD), intracellular NFTs (iNFTs) develop along with extracellular beta-amyloid (Abeta) deposits. Reports on whether NFTs have Abeta associated with them are inconsistent. Here we study NFTs and their direct relationship with Abeta-like fragments in cases of AD, Down Syndrome, and the parkinsonism-dementia complex of Guam, using a panel of antibodies which recognize different epitopes of Abeta. In all diseases, as well as in the aged controls, the majority of extracellular NFTs (eNFTs) are stained with antibodies recognizing the 40 carboxy-terminal of Abeta, but not other epitopes. Such staining is morphologically distinguishable from the previously described Abeta positive 'tangle associated amyloid deposits' (TAADs), which surround some eNFTs, and are immunopositive for all epitopes of the Abeta molecule. Some iNFTs are immunoreactive with antibodies to the 42 carboxy-terminal epitope, and, to a lesser extent, with antibodies to midportions and more N-terminal epitopes of Abeta. These results may indicate a direct interaction between Abeta and NFTs, although secondary deposition or crossreactivity with other epitopes associated with NFTs cannot be ruled out.
神经原纤维缠结（NFTs）在多种神经退行性疾病中形成。在阿尔茨海默病（AD）中，细胞内NFTs（iNFTs）与细胞外β-淀粉样蛋白（Aβ）沉积同时出现。关于NFTs是否与Aβ相关的报道并不一致。在此，我们使用一组识别Aβ不同表位的抗体，研究AD、唐氏综合征和关岛帕金森病痴呆综合征病例中NFTs及其与Aβ样片段的直接关系。在所有疾病以及老年对照中，大多数细胞外NFTs（eNFTs）被识别Aβ 40羧基末端的抗体染色，但不被其他表位染色。这种染色在形态上与先前描述的Aβ阳性“缠结相关淀粉样沉积”（TAADs）不同，TAADs围绕一些eNFTs，并且对Aβ分子的所有表位呈免疫阳性。一些iNFTs与针对42羧基末端表位的抗体发生免疫反应，并且在较小程度上与针对Aβ中间部分和更多N末端表位的抗体发生免疫反应。这些结果可能表明Aβ与NFTs之间存在直接相互作用，尽管不能排除与NFTs相关的其他表位的二次沉积或交叉反应。
