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Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease
Liu L, Lauro BM, He A, Lee H, Bhattarai S, Wolfe MS, Bennett DA, Karch CM et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022-03-12
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Introduction Identifying CSF-based biomarkers for the β-amyloidosis that initiates Alzheimer's disease (AD) could provide inexpensive and dynamic tests to distinguish AD from normal aging and predict future cognitive decline. Methods We developed immunoassays specifically detecting all C-terminal variants of secreted amyloid β-protein and identified a novel biomarker, the Aβ 37/42 ratio, that outperforms the canonical Aβ42/40 ratio as a means to evaluate the γ-secretase activity and brain Aβ accumulation. Results We show that Aβ 37/42 can distinguish physiological and pathological status in (1) presenilin-1 mutant vs wild-type cultured cells, (2) AD vs control brain tissue, and (3) AD versus cognitively normal (CN) subjects in CSF, where 37/42 (AUC 0.9622) outperformed 42/40 (AUC 0.8651) in distinguishing CN from AD. Discussion We conclude that the Aβ 37/42 ratio sensitively detects presenilin/γ-secretase dysfunction and better distinguishes CN from AD than Aβ42/40 in CSF. Measuring this novel ratio alongside promising phospho-tau analytes may provide highly discriminatory fluid biomarkers for AD.
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APA 7th
Liu, L., Lauro, B. M., He, A., Lee, H., Bhattarai, S., Wolfe, M. S., et al. (2023). Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.12646
Vancouver
Liu L, Lauro BM, He A, Lee H, Bhattarai S, Wolfe MS, et al. Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. doi:10.1002/alz.12646. PMID: 35278341.
BibTeX
@article{liu2023-35278341,
author = {Liu, L. and Lauro, B. M. and He, A. and Lee, H. and Bhattarai, S. and Wolfe, M. S. and Bennett, D. A. and Karch, C. M. and others},
title = {{Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2023},
doi = {10.1002/alz.12646},
pmid = {35278341},
url = {https://doi.org/10.1002/alz.12646}
}
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Key findings
- Results We show that Aβ 37/42 can distinguish physiological and pathological status in (1) presenilin-1 mutant vs wild-type cultured cells, (2) AD vs control brain tissue, and (3) AD versus cognitively normal (CN) subjects in CSF, where 37/42 (AUC 0.9622) outperformed 42/40 (AUC 0.8651) in distinguishing CN from AD.
- Discussion We conclude that the Aβ 37/42 ratio sensitively detects presenilin/γ-secretase dysfunction and better distinguishes CN from AD than Aβ42/40 in CSF.
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Study details
- Effect sizeAUC 0.9622; AUC 0.8651
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35278341) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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