| First Author | Schieb H | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 39 | Pages | 33747-58 |
| PubMed ID | 21795681 | Mgi Jnum | J:176737 |
| Mgi Id | MGI:5292592 | Doi | 10.1074/jbc.M111.246561 |
| Citation | Schieb H, et al. (2011) {beta}-Amyloid Peptide Variants in Brains and Cerebrospinal Fluid from Amyloid Precursor Protein (APP) Transgenic Mice: COMPARISON WITH HUMAN ALZHEIMER AMYLOID. J Biol Chem 286(39):33747-58 |
| abstractText | In this study, we report a detailed analysis of the different variants of amyloid-beta (Abeta) peptides in the brains and the cerebrospinal fluid from APP23 transgenic mice, expressing amyloid precursor protein with the Swedish familial Alzheimer disease mutation, at different ages. Using one- and two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry, we identified the Abeta peptides Abeta(1-40), -(1-42), -(1-39), -(1-38), -(1-37), -(2-40), and -(3-40) as well as minor amounts of pyroglutamate-modified Abeta (Abeta(N3pE)) and endogenous murine Abeta in brains from 24-month-old mice. Chemical modifications of the N-terminal amino group of Abeta were identified that had clearly been introduced during standard experimental procedures. To address this issue, we additionally applied amyloid extraction in ultrapure water. Clear differences between APP23 mice and Alzheimer disease (AD) brain samples were observed in terms of the relative abundance of specific variants of Abeta peptides, such as Abeta(N3pE), Abeta(1-42), and N-terminally truncated Abeta(2/3-42). These differences to human AD amyloid were also noticed in a related mouse line transgenic for human wild type amyloid precursor protein. Taken together, our findings suggest different underlying molecular mechanisms driving the amyloid deposition in transgenic mice and AD patients. |
