Maddalena Alessia S, Papassotiropoulos Andreas, Gonzalez-Agosti Charo, Signorell Andri, Hegi Thomas, Pasch Thomas, Nitsch Roger M, Hock Christoph
Division of Psychiatry Research, University of Zürich, Zürich, Switzerland.
Neurodegener Dis. 2004;1(4-5):231-5. doi: 10.1159/000080991.
Amyloid-beta peptides (Abeta) are major components of amyloid plaques in the Alzheimer's disease (AD) brain and have been proposed as diagnostic markers in cerebrospinal fluid (CSF). Abeta derived from brain may be processed into fragments before emerging in CSF. Therefore, we determined mass profiles of Abeta peptides in CSF of patients with AD and age-matched healthy control subjects (CTR) by using protein biochip technology. Abeta peptides were captured on the chip surfaces (spots) by the specific monoclonal antibody 6E10 and were then analyzed by integrated surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS). We found Abeta species with mean molecular masses at 1,583.3 Da (corresponding to Abeta2-14), 2,068.5 Da (Abeta1-17), 2,166.4 Da (Abeta1-18), 3,676.6 Da (Abeta1-33), 3,789.4 Da (Abeta1-34), 4,076.9 Da (Abeta1-37), 4,134.0 Da (Abeta1-38), 4,233.3 Da (Abeta1-39), 4,332.4 Da (Abeta1-40) and 4,516.8 Da (Abeta1-42) in both AD (n = 24) and CTR (n = 24) subjects. Abeta1-38 appeared to be a major Abeta species in human CSF along with Abeta1-40. Quantitation revealed that CSF levels of Abeta1-38 were significantly decreased in AD as compared to CTR subjects. The CSF profile of Abeta peptides may be used for diagnostic and therapeutic purposes in clinical studies.
β-淀粉样肽（Aβ）是阿尔茨海默病（AD）脑内淀粉样斑块的主要成分，并已被提议作为脑脊液（CSF）中的诊断标志物。源自脑内的Aβ在出现在脑脊液之前可能会被加工成片段。因此，我们使用蛋白质生物芯片技术测定了AD患者和年龄匹配的健康对照受试者（CTR）脑脊液中Aβ肽的质量谱。Aβ肽通过特异性单克隆抗体6E10捕获在芯片表面（斑点）上，然后通过集成表面增强激光解吸电离飞行时间质谱（SELDI-TOF-MS）进行分析。我们在AD患者（n = 24）和CTR受试者（n = 24）中均发现了平均分子量分别为1583.3 Da（对应于Aβ2-14）、2068.5 Da（Aβ1-17）、2166.4 Da（Aβ1-18）、3676.6 Da（Aβ1-33）、3789.4 Da（Aβ1-34）、4076.9 Da（Aβ1-37）、4134.0 Da（Aβ1-38）、4233.3 Da（Aβ1-39）、4332.4 Da（Aβ1-40）和4516.8 Da（Aβ1-42）的Aβ种类。Aβ1-38似乎是人类脑脊液中与Aβ1-40一起的主要Aβ种类。定量分析显示，与CTR受试者相比，AD患者脑脊液中Aβ1-38的水平显著降低。Aβ肽的脑脊液谱可用于临床研究中的诊断和治疗目的。
