An Alzheimer's disease-specific β-amyloid fragment signature in cerebrospinal fluid

Pathogenic events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of the neurotoxic P-amyloid peptide (A beta), especially the 42 amino acid peptide A beta 1-42. While much is known about the production of A beta 1-42, many questions remain about how the peptide is degraded. To investigate the degradation pattern, we developed a method based on immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry that determines the A beta degradation fragment pattern in cerebrospinal fluid (CSF). We found in total 18 C-terminally and 2 N-terminally truncated A beta peptides and preliminary data indicated that there were differences in the detected A beta relative abundance pattern between AD and healthy controls. Here, we provide direct evidence that an A beta fragment signature consisting of A beta 1-16, A beta 1-33, A beta 1-39, and A beta 1-42 in CSF distinguishes sporadic AD patients from non-demented controls with an overall accuracy of 86%. (c) 2006 Elsevier Ireland Ltd. All rights reserved.