Palmert M R, Usiak M, Mayeux R, Raskind M, Tourtellotte W W, Younkin S G
Division of Neuropathology, Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Neurology. 1990 Jul;40(7):1028-34. doi: 10.1212/wnl.40.7.1028.
We isolated and sequenced a soluble approximately 25 kDa amino-terminal derivative of the beta amyloid protein precursor (beta APP) that is readily detected in human cerebrospinal fluid (CSF). In CSF samples from 24 Alzheimer's disease (AD) patients and 12 controls, we then quantitated this approximately 25 kDa form as well as the approximately 125 and approximately 105 kDa derivatives that we previously identified. Our analysis shows (1) that, in AD, there is a significant decrease in the relative amount of the approximately 105 kDa form and a corresponding significant increase in the relative amount of the approximately 25 kDa form; (2) that these changes correlate with the mental status of the AD patients; and (3) that the same changes occur to a lesser extent in elderly as compared with young control patients. These observations indicate that processing of the beta APP changes in normal individuals as they age and to a greater extent in those who develop AD. The changes in beta APP derivatives that we have observed in CSF could have major implications because they may reflect fundamental mechanisms responsible for amyloid deposition and can be measured in living patients.
我们分离并测序了一种可溶性的、分子量约为25 kDa的β淀粉样蛋白前体（βAPP）氨基末端衍生物，该衍生物在人脑脊液（CSF）中易于检测到。然后，在24例阿尔茨海默病（AD）患者和12例对照的脑脊液样本中，我们对这种分子量约为25 kDa的形式以及我们之前鉴定出的分子量约为125 kDa和105 kDa的衍生物进行了定量分析。我们的分析表明：（1）在AD患者中，分子量约为105 kDa的形式相对含量显著降低，而分子量约为25 kDa的形式相对含量相应显著增加；（2）这些变化与AD患者的精神状态相关；（3）与年轻对照患者相比，老年人中同样的变化程度较小。这些观察结果表明，βAPP的加工过程在正常个体随年龄增长时会发生变化，而在患AD的个体中变化程度更大。我们在脑脊液中观察到的βAPP衍生物的变化可能具有重要意义，因为它们可能反映了淀粉样蛋白沉积的基本机制，并且可以在活体患者中进行测量。
