Amyloid β peptides in cerebrospinal fluid as profiled with surface enhanced laser desorption/ionization time-of-flight mass spectrometry:: Evidence of novel biomarkers in Alzheimer's disease

Background: The advent of new therapeutic avenues for Alzheimer's disease (AD) calls for an improved early and differential diagnosis. Methods: With surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), cerebrospinal fluid from patients with AD (n = 10) and nondemented control subjects (n = 9) was studied. Results: Molecular mass signals were observed corresponding to three novel amyloid beta (Abeta) peptides that have not previously been described, in addition to those previously known, with molecular masses of 4525.1 d, 4846.8 d, and 7755.8 d. The signal-to-noise ratios (S/NR) of Abeta (4525.1) and Abeta (7758.8+ 2H) were significantly decreased in AD [Abeta (4525.1): median 2.2 and 4.3 in AD and control subjects, respectively, p < .01; Abeta (7758.8+ 2H): median 1.0 and 14.0 in AD and control subjects, respectively, p < .01], whereas the S/NR of Abeta (4846.8) was significantly increased in AD (median 3.6 and 2.5 in AD and control subjects, respectively, p < .05). The S/NR of two known AD biomarkers, Abeta 1-42 and Abeta 1-40, expectedly turned out to be significantly decreased (p < . 01) and unaltered in AD, respectively. A moderate and highly significant correlation was observed between S/NR of Abeta 1-42 and Abeta 42 concentration as measured with enzyme-linked immunosorbent assay (R = .67, p < .01). Conclusions: We report evidence of three novel amyloid beta peptides that might play an important role in the diagnosis and pathophysiology of Alzheimer's disease.