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Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients
Li R, Lindholm K, Yang LB, Yue X, Citron M, Yan R, Beach T, Sue L et al.. Proceedings of the National Academy of Sciences of the United States of America, 2004-02-20
Topic: Amyloid, tau and blood-test diagnosis
Whether elevated beta-secretase (BACE) activity is related to plaque formation or amyloid beta peptide (Abeta) production in Alzheimer's disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various Abeta species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the Abeta species detected in rapidly autopsied brains (<3 h) with sporadic AD were Abeta(1-x) and Abeta(1-42), as well as Abeta(x-42). To establish a linkage between Abeta levels and BACE, we examined BACE protein, mRNA expression and enzymatic activity in the same brain region of AD brains. We found that both BACE mRNA and protein expression is elevated in vivo in the frontal cortex. The elevation of BACE enzymatic activity in AD is correlated with brain Abeta(1-x) and Abeta(1-42) production. To examine whether BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and performed allelic association analysis. We found no mutations in the ORF of the BACE gene. Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid precursor protein-transfected cells. These findings demonstrate correlation between Abeta loads and BACE elevation and also suggest that as a consequence, BACE elevation may lead to increased Abeta production and enhanced deposition of amyloid plaques in sporadic AD patients.
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APA 7th
Li, R., Lindholm, K., Yang, L. B., Yue, X., Citron, M., Yan, R., et al. (2004). Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.0205689101
Vancouver
Li R, Lindholm K, Yang LB, Yue X, Citron M, Yan R, et al. Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients. Proceedings of the National Academy of Sciences of the United States of America. 2004. doi:10.1073/pnas.0205689101. PMID: 14978286.
BibTeX
@article{li2004-14978286,
author = {Li, R. and Lindholm, K. and Yang, L. B. and Yue, X. and Citron, M. and Yan, R. and Beach, T. and Sue, L. and others},
title = {{Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2004},
doi = {10.1073/pnas.0205689101},
pmid = {14978286},
url = {https://doi.org/10.1073/pnas.0205689101}
}
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Key findings
- We found that most of the Abeta species detected in rapidly autopsied brains (<3 h) with sporadic AD were Abeta(1-x) and Abeta(1-42), as well as Abeta(x-42).
- We found that both BACE mRNA and protein expression is elevated in vivo in the frontal cortex.
- We found no mutations in the ORF of the BACE gene.
- Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid precursor protein-transfected cells.
- These findings demonstrate correlation between Abeta loads and BACE elevation and also suggest that as a consequence, BACE elevation may lead to increased Abeta production and enhanced deposition of amyloid plaques in sporadic AD patients.
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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 (Proceedings of the National Academy of Sciences of the United States of America) |
| 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 | 2004 — 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 14978286) |
| 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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