BACKGROUND: Proteolytic degradation of amyloid b (Ab) peptides has been intensely studied due to the central role of Ab in @entity195 ( @entity195 ) pathogenesis. While several enzymes have been shown to degrade Ab peptides, the main pathway of Ab degradation in vivo is unknown. Cerebrospinal fluid (CSF) Ab42 is reduced in @entity195 , reflecting aggregation and deposition in the brain, but low CSF Ab42 is, for unknown reasons, also found in some inflammatory @entity75 such as @entity4008 . METHOD: Using @entity14682 -labeling mass spectrometry and immune-affinity purification, we examined endogenous proteolytic processing of Ab in @entity1 CSF. RESULTS: The Ab peptide profile was stable in CSF samples from healthy controls but in CSF samples from @entity1 with @entity4008 , showing increased leukocyte cell count, @entity14682 -labeling mass spectrometry identified proteolytic activities degrading Ab into several short fragments, including abundant Ab1-19 and 1-20. After antibiotic treatment, no degradation of Ab was detected. In vitro experiments located the source of the proteolytic activity to blood components, including leukocytes and erythrocytes, with @entity12056 as the likely protease. A recombinant version of the mid-domain anti-Ab antibody solanezumab was found to inhibit @entity12056 -mediated Ab degradation. CONCLUSION: @entity14682 labeling-mass spectrometry can be used to detect endogenous proteolytic activity in @entity1 CSF. Using this technique, we found an enzymatic activity that was identified as @entity12056 that cleaves Ab in the mid-domain of the peptide, and could be inhibited by a recombinant version of the mid-domain anti-Ab antibody solanezumab.

Ex vivo XXXX -labeling mass spectrometry identifies a peripheral amyloid b clearance pathway.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity12056 :: ('3416', 'Gene') :: ['insulin-degrading enzyme'] @entity4008 :: ('MESH:D016920', 'Disease') :: ['bacterial meningitis'] @entity75 :: ('MESH:D001927', 'Disease') :: ['brain disorders'] @entity14682 :: ('CHEBI:33815', 'Chemical') :: ['(18)O'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"]
@entity14682 :: (CHEBI:33815,Chemical) :: ['(18)O']
