Palmert M R, Siedlak S L, Podlisny M B, Greenberg B, Shelton E R, Chan H W, Usiak M, Selkoe D J, Perry G, Younkin S G
Division of Neuropathology, Case Western Reserve University School of Medicine, Cleveland OH 44106.
Biochem Biophys Res Commun. 1989 Nov 30;165(1):182-8. doi: 10.1016/0006-291x(89)91052-8.
The amyloid deposited in Alzheimer's disease (AD) is composed primarily of a 39-42 residue polypeptide (beta AP) that is derived from a larger beta amyloid protein precursor (beta APP). In previous studies, we and others identified full-length, membrane-associated forms of the beta APP and showed that these forms are processed into soluble derivatives that lack the carboxyl-terminus of the full-length forms. In this report, we demonstrate that the soluble approximately 125 and approximately 105 kDa forms of the beta APP found in human cerebrospinal fluid are specifically labeled by several different antisera to the beta AP. This finding indicates that both soluble derivatives contain all or part of the beta AP sequence, and it suggests that one or both of these forms may be the immediate precursor of the amyloid deposited in AD.
阿尔茨海默病(AD)中沉积的淀粉样蛋白主要由一种39 - 42个残基的多肽(β-淀粉样蛋白,β-AP)组成,该多肽源自一种更大的β-淀粉样蛋白前体(β-淀粉样前体蛋白,β-APP)。在先前的研究中,我们及其他研究人员鉴定出了全长的、与膜相关的β-APP形式,并表明这些形式会被加工成缺乏全长形式羧基末端的可溶性衍生物。在本报告中,我们证明在人类脑脊液中发现的可溶性约125 kDa和约105 kDa的β-APP形式被几种针对β-AP的不同抗血清特异性标记。这一发现表明这两种可溶性衍生物都包含全部或部分β-AP序列,并且表明这些形式中的一种或两种可能是AD中沉积的淀粉样蛋白的直接前体。