Brion J P
Laboratory of Pathology and Electron Microscopy, Université Libre de Bruxelles, Brussels.
Biochim Biophys Acta. 1992 Nov 10;1160(1):134-42. doi: 10.1016/0167-4838(92)90047-h.
The two characteristic neuropathological lesions of Alzheimer's disease are the neurofibrillary tangles and the senile plaques. Neurofibrillary tangles are made of abnormal filaments (PHF) accumulating in neurons and mainly composed of a modified form of the microtubule-associated protein tau (PHF-tau). Senile plaques are composed of a cluster of dystrophic neurites surrounding an extracellular deposit of amyloid fibers made of a 42 amino-acid peptide (beta-amyloid peptide). The abnormal filaments contain the complete sequences of the different tau isoforms. The PHF-tau proteins can be distinguished from the normal tau proteins by the presence of several phosphorylated sites. One of these sites is phosphorylated by a calcium-calmodulin-dependent kinase. The relationship between PHF-tau and the cytoskeletal pathology in Alzheimer's disease is further discussed.
阿尔茨海默病的两个典型神经病理学病变是神经原纤维缠结和老年斑。神经原纤维缠结由在神经元中积累的异常细丝（PHF）组成，主要由微管相关蛋白tau的一种修饰形式（PHF-tau）构成。老年斑由围绕由42个氨基酸肽（β-淀粉样肽）构成的淀粉样纤维细胞外沉积物的营养不良性神经突簇组成。异常细丝包含不同tau异构体的完整序列。PHF-tau蛋白可通过存在多个磷酸化位点与正常tau蛋白区分开来。这些位点之一由钙调蛋白依赖性激酶磷酸化。进一步讨论了PHF-tau与阿尔茨海默病细胞骨架病理学之间的关系。
