Biochimie 113 (2015) 86 – 92
Magnus Rogeberg a, b, *, Marianne Wettergreen a, b, Lars N.G. Nilsson c, Tormod Fladby a, d
a Department of Neurology, Akershus University Hospital, Lørenskog, Norway
b Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital and University of Oslo, Norway
c Department of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, Norway
d Department of Neurology, Faculty Division, Akershus University Hospital and University of Oslo, Lørenskog, Norway
Amyloid beta (Ab) 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 Ab in AD brain may be caused by altered Ab metabolism, including reduced enzymatic degradation. Our previous enzymatic study of Ab degradation revealed that intracellular enzymes produced several truncated Ab mid-domain fragments. We therefore generated an antibody to enable identification of these anticipated Ab species in cerebrospinal fluid (CSF). The produced antibody displayed affinity for the Ab mid-domain region and 36 N-terminally truncated Ab fragments were precipitated from human CSF and identified by liquid chromatography e mass spectrometry. 31 peptides were truncated from residue 18 up to 23, Nterminal 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 Ab degradation profile.