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

Amyloid beta (Aβ) 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 Aβ in AD brain may be caused by altered Aβ metabolism, including reduced enzymatic degradation. Our previous enzymatic study of Aβ degradation revealed that intracellular enzymes produced several truncated Aβ mid-domain fragments. We therefore generated an antibody to enable identification of these anticipated Aβ species in cerebrospinal fluid (CSF). The produced antibody displayed affinity for the Aβ mid-domain region and 36 N-terminally truncated Aβ 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 Aβ degradation profile.