Cerebrospinal Fluid Profile of Amyloid beta Peptides in Patients with Alzheimer's Disease Determined by Protein Biochip Technology

Amyloid-beta peptides (A beta) are major components of amyloid plaques in the Alzheimer's disease (AD) brain and have been proposed as diagnostic markers in cerebrospinal fluid (CSF). A beta derived from brain may be processed into fragments before emerging in CSF. Therefore, we determined mass profiles of A beta peptides in CSF of patients with AD and age-matched healthy control subjects (CTR) by using protein biochip technology. A beta 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 A beta species with mean molecular masses at 1,583.3 Da (corresponding to A beta(2-14)), 2,068.5 Da (A beta(1-17)), 2,166.4 Da (A beta(1-18)), 3,676.6 Da (A beta(1-33)), 3,789.4 Da (A beta(1-34)), 4,076.9 Da (A beta(1-37)), 4,134.0 Da (A beta(1-38)), 4,233.3 Da (A beta(1-39)), 4,332.4 Da (A beta(1-40)) and 4,516.8 Da (A beta(1-42)) in both AD (n = 24) and CTR (n = 24) subjects. A beta(1-38) appeared to be a major A beta species in human CSF along with A beta(1-40). Quantitation revealed that CSF levels of A beta(1-38) were significantly decreased in AD as compared to CTR subjects. The CSF profile of A beta peptides may be used for diagnostic and therapeutic purposes in clinical studies. Copyright (C) 2004 S. Karger AG, Basel