Identification of amyloid beta mid-domain fragments in human cerebrospinal fluid

Amyloid beta (A beta) is a peptide derived from processing of the membrane bound amyloid precursor protein and is a main constituent in amyloid plaques in Alzheimer's disease (AD). The excess A beta in AD brain may be caused by altered A beta metabolism, including reduced enzymatic degradation. Our previous enzymatic study of A beta degradation revealed that intracellular enzymes produced several truncated A beta mid-domain fragments. We therefore generated an antibody to enable identification of these anticipated A beta species in cerebrospinal fluid (CSF). The produced antibody displayed affinity for the A beta mid-domain region and 36 N-terminally truncated A beta fragments were precipitated from human CSF and identified by liquid chromatography - mass spectrometry. 31 peptides were truncated from residue 18 up to 23, N-terminal truncation that have not previously been identified in CSF. The results show that the complexity of amyloid beta peptides circulating in the CSF is greater than previously suggested and we also demonstrate that the mid-domain antibody used can serve as an additional tool for mapping a more complete A beta degradation profile. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.