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

Abstract

Amyloid-β peptides (Aβ) are major components of amyloid plaques in the Alzheimer’s disease (AD) brain and have been proposed as diagnostic markers in cerebrospinal fluid (CSF). Aβ derived from brain may be processed into fragments before emerging in CSF. Therefore, we determined mass profiles of Aβ peptides in CSF of patients with AD and age-matched healthy control subjects (CTR) by using protein biochip technology. Aβ 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 Aβ species with mean molecular masses at 1,583.3 Da (corresponding to Aβ_2–14), 2,068.5 Da (Aβ_1–17), 2,166.4 Da (Aβ_1–18), 3,676.6 Da (Aβ_1–33), 3,789.4 Da (Aβ_1–34), 4,076.9 Da (Aβ_1–37), 4,134.0 Da (Aβ_1–38), 4,233.3 Da (Aβ_1–39), 4,332.4 Da (Aβ_1–40) and 4,516.8 Da (Aβ_1–42) in both AD (n = 24) and CTR (n = 24) subjects. Aβ_1–38 appeared to be a major Aβ species in human CSF along with Aβ_1–40. Quantitation revealed that CSF levels of Aβ_1–38 were significantly decreased in AD as compared to CTR subjects. The CSF profile of Aβ peptides may be used for diagnostic and therapeutic purposes in clinical studies.