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.

Highlights

  • A major neuropathological feature of Alzheimer’s disease (AD)1 is the presence of senile plaques in the brain

  • Establishment and Characterization of Monoclonal Antibodies against ␤A4 —In order to obtain monoclonal antibodies (mAbs) which are specific for the different C termini of short-tailed and long-tailed ␤A4, we immunized two mice with synthetic ␤A4 33– 40 peptide and four mice with synthetic ␤A4 35– 42 peptide, both conjugated to carrier protein

  • Amyloid deposition in the form of senile plaques is a central feature of AD pathology, the source of ␤A4 in the deposits is not known

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Summary

Introduction

A major neuropathological feature of Alzheimer’s disease (AD)1 is the presence of senile plaques in the brain. Besides the 4-kDa full-length ␤A4 band, we could detect several N-terminal variants of ␤A4 in CSF and plasma of both AD patients and controls.

Results
Conclusion

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