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| Analysis of heterogeneous beta A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay |
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| Author(s): Ida N, Hartmann T, Pantel J, Schroder J, Zerfass R, Forstl H, Sandbrink R, Masters CL, Beyreuther K |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 271 Issue: 37 Pages: 22908-22914 Published: SEP 13 1996 |
| Times Cited: 323 References: 46 |
| Abstract: The beta A4 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 beta A4 1-40 is the major form produced by cell metabolism and found in CSF, recent observations suggest that the long-tailed beta A4 1-42 plays a more crucial role in AD pathogenesis. Here, we established new monoclonal antibodies against the C-terminal end of beta A4 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 beta A4, and both beta A4 1-40 and 1-42 levels in CSF could be determined by direct loading of the samples. flood levels of beta A4 1-40 and 1-42 were also determined by specific immunoprecipitation followed by Western blot detection. We found that CSF beta A4 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 beta A4 1-40 in CSF, and of beta A4 1-40 as well as beta A4 1-42 in plasma, were not different between AD patients and controls. Besides the 4-kDa full-length beta A4 band, we could also detect several N-terminal variants of beta A4 in CSF and plasma of both AD patients and controls. Two N-terminally truncated beta A4 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 beta A4 is different in these two compartments. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV HEIDELBERG, CTR MOL BIOL HEIDELBERG, D-69120 HEIDELBERG, GERMANY
2. UNIV HEIDELBERG, PSYCHIAT CLIN, D-69115 HEIDELBERG, GERMANY
3. CENT INST MENTAL HLTH, D-69159 MANNHEIM, GERMANY
4. UNIV MELBOURNE, DEPT PATHOL, PARKVILLE, VIC 3052 AUSTRALIA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: VG672 |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |