Abstract |
The betaA4 peptide, a major component of senile plaques in Alzheimer's disease (AD) brain, has been found in cerebrospinal fluid (CSF) and blood of both AD patients and normal subjects. Although betaA4 1-40 is the major form produced by cell metabolism and found in CSF, recent observations suggest that the long-tailed betaA4 1-42 plays a more crucial role in AD pathogenesis. Here, we established new monoclonal antibodies against the C-terminal end of betaA4 1-40 and 1-42, and used them for the specific Western blot detection. After optimizing the assay conditions, these antibodies detected low picogram amount of betaA4, and both betaA4 1-40 and 1-42 levels in CSF could be determined by direct loading of the samples. Blood levels of betaA4 1-40 and 1-42 were also determined by specific immunoprecipitation followed by Western blot detection. We found that CSF betaA4 1-42 level is lower in AD patients compared with non-demented controls, although there was a significant overlap between the groups. The level of betaA4 1-40 in CSF, and of betaA4 1-40 as well as betaA4 1-42 in plasma, were not different between AD patients and controls. Besides the 4-kDa full-length betaA4 band, we could also detect several N-terminal variants of betaA4 in CSF and plasma of both AD patients and controls. Two N-terminally truncated betaA4 species migrating at the position of 3.3 and 3.7 kDa were found in CSF, while 3.7- and 5-kDa forms were found in plasma. The relative abundance of these various species were considerably different in the CSF and plasma, suggesting that the cellular source and/or clearance of betaA4 is different in these two compartments.
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Authors | N Ida, T Hartmann, J Pantel, J Schröder, R Zerfass, H Förstl, R Sandbrink, C L Masters, K Beyreuther |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 271
Issue 37
Pg. 22908-14
(Sep 13 1996)
ISSN: 0021-9258 [Print] United States |
PMID | 8798471
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Protein Precursor
- Antibodies, Monoclonal
- Peptide Fragments
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Topics |
- Aged
- Aged, 80 and over
- Amyloid beta-Protein Precursor
(analysis, blood, cerebrospinal fluid)
- Antibodies, Monoclonal
- Blotting, Western
(methods)
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Male
- Peptide Fragments
(analysis)
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