Cerebrospinal fluid profile of amyloid beta peptides in patients with Alzheimer's disease determined by protein biochip technology

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.