Title : An online nano-LC-
ESI-FTICR-MS method for comprehensive characterization of endogenous
fragments from amyloid β and
amyloid precursor protein in human and cat cerebrospinal fluid
Abstract :
- Amyloid precursor protein ( APP ) is the precursor protein to amyloid β ( Aβ) , the main constituent of senile plaques in Alzheimer's disease (AD)
- Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology
- When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications ( PTMs ) within the N-terminal half of the peptide
- However, by using electron capture dissociation ( ECD ), we obtained a more comprehensive sequence coverage for several APP / Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs
- Abnormal APP / Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat
- By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified
- Further, sialylated core 1 like O-glycans at Tyr10 , recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid ( CSF )
- It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria
- We here describe a detailed characterization of endogenous APP / Aβ peptide species in CSF by using an online top-down MS-based method
Output (sent_index, trigger,
protein,
sugar,
site):
- 7. Tyr10, , -, O-glycans, Tyr10
- 7. sialylated, , -, sialylated core 1, -
Output(Part-Of) (sent_index,
protein,
site):
- 0. amyloid precursor protein, fragments
- 2. Endogenous Aβ , peptides
- 3. Aβ , peptides
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 7. amyloid precursor protein, O-glycans, Tyr10