Lalowski M, Golabek A, Lemere C A, Selkoe D J, Wisniewski H M, Beavis R C, Frangione B, Wisniewski T
Department of Pathology, New York University Medical Center, New York, New York 10016, USA.
J Biol Chem. 1996 Dec 27;271(52):33623-31. doi: 10.1074/jbc.271.52.33623.
Down's syndrome (DS) patients show accelerated Alzheimer's disease (AD) neuropathology, which consists of preamyloid lesions followed by the development of neuritic plaques and neurofibrillary tangles. The major constituents of preamyloid and neuritic plaques are amyloid beta (Abeta) peptides. Preamyloid lesions are defined as being Abeta immunoreactive lesions, which unlike neuritic plaque amyloid are Congo red-negative and largely nonfibrillar ultrastructurally. DS patients can develop extensive preamyloid deposits in the cerebellum, without neuritic plaques; hence, DS cerebellums are a source of relatively pure preamyloid. We biochemically characterized the composition of DS preamyloid and compared it to amyloid in the neuritic plaques and leptomeninges in the same patients. We found that Abeta17-42 or p3 is a major Abeta peptide of DS cerebellar preamyloid. This 26-residue peptide is also present in low quantities in neuritic plaques. We suggest that preamyloid can now be defined biochemically as lesions in which a major Abeta peptide is p3.
唐氏综合征（DS）患者表现出阿尔茨海默病（AD）神经病理学的加速发展，其包括淀粉样前体病变，随后是神经炎性斑块和神经原纤维缠结的形成。淀粉样前体和神经炎性斑块的主要成分是β淀粉样蛋白（Aβ）肽。淀粉样前体病变被定义为Aβ免疫反应性病变，与神经炎性斑块淀粉样蛋白不同，其刚果红染色阴性，在超微结构上基本无纤维状。DS患者可在小脑形成广泛的淀粉样前体沉积物，而无神经炎性斑块；因此，DS小脑是相对纯净的淀粉样前体的来源。我们对DS淀粉样前体的组成进行了生化特征分析，并将其与同一患者神经炎性斑块和软脑膜中的淀粉样蛋白进行了比较。我们发现Aβ17 - 42或p3是DS小脑淀粉样前体的主要Aβ肽。这种26个氨基酸残基的肽在神经炎性斑块中也少量存在。我们认为，现在可以从生化角度将淀粉样前体定义为主要Aβ肽为p3的病变。
