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Updated: Apr 15, 2026
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Identification of amyloid beta mid-domain fragments in human cerebrospinal fluid
Magnus Rogeberg1, Marianne Wettergreen1, Lars N G Nilsson2
1Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital and University of Oslo, Norway.
Abstract:
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.
Insights
Researchers identified novel truncated amyloid beta (Aβ) fragments in cerebrospinal fluid (CSF), suggesting greater Aβ peptide complexity in Alzheimer's disease (AD). A new mid-domain antibody aids in mapping Aβ degradation profiles.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Amyloid beta (Aβ) peptides accumulate in Alzheimer's disease (AD) amyloid plaques.
- Altered Aβ metabolism, including reduced enzymatic degradation, may contribute to excess Aβ in the AD brain.
Purpose of the Study:
- To identify novel truncated Aβ fragments in human cerebrospinal fluid (CSF).
- To characterize the complexity of Aβ peptides circulating in CSF.
- To validate a novel mid-domain antibody for mapping Aβ degradation.
Main Methods:
- Generation of a specific antibody targeting the Aβ mid-domain.
- Precipitation of Aβ fragments from human CSF using the antibody.
- Identification of precipitated peptides via liquid chromatography-mass spectrometry (LC-MS).
Main Results:
- 36 N-terminally truncated Aβ fragments were identified in human CSF.
- 31 of these peptides exhibited truncations from residue 18 up to 23, previously unidentified in CSF.
- The study demonstrates greater complexity of Aβ peptides in CSF than previously known.
Conclusions:
- The complexity of amyloid beta peptides in CSF is significantly greater than previously understood.
- The developed mid-domain antibody is a valuable tool for comprehensive Aβ degradation profiling.
- Further research into these novel fragments may offer new insights into AD pathogenesis.
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