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Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay
Ida N, Hartmann T, Pantel J, Schröder J, Zerfass R, Förstl H, Sandbrink R, Masters CL et al.. The Journal of biological chemistry, 1996-09-01
Topic: Plasma and spinal-fluid biomarkers
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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APA 7th
Ida, N., Hartmann, T., Pantel, J., Schröder, J., Zerfass, R., Förstl, H., et al. (1996). Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. The Journal of biological chemistry. https://doi.org/10.1074/jbc.271.37.22908
Vancouver
Ida N, Hartmann T, Pantel J, Schröder J, Zerfass R, Förstl H, et al. Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. The Journal of biological chemistry. 1996. doi:10.1074/jbc.271.37.22908. PMID: 8798471.
BibTeX
@article{ida1996-8798471,
author = {Ida, N. and Hartmann, T. and Pantel, J. and Schröder, J. and Zerfass, R. and Förstl, H. and Sandbrink, R. and Masters, C. L. and others},
title = {{Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay}},
journal = {The Journal of biological chemistry},
year = {1996},
doi = {10.1074/jbc.271.37.22908},
pmid = {8798471},
url = {https://doi.org/10.1074/jbc.271.37.22908}
}
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Key findings
- 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.
- 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 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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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1996 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8798471) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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