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Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum
Trelle AN, Young CB, Vossler H, Ramos Benitez J, Cody KA, Mendiola JH, Swarovski MS, Guen YL et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-12-23
Topic: Amyloid, tau and blood-test diagnosis
Introduction The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation. Methods We evaluated fully-automated Lumipulse plasma Aβ 42 /Aβ 40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ 42 /Aβ 40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined. Results Plasma Aβ 42 /Aβ 40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ 42 /Aβ 40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ 42 /Aβ 40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation. Discussion Lumipulse plasma Aβ 42 /Aβ 40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum. Highlights Lumipulse plasma amyloid beta (Aβ) 42 /Aβ 40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ 42 /Aβ 40 over time. Plasma Aβ 42 /Aβ 40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ 42 /Aβ 40 was sensitive to memory and tau burden in clinically unimpaired older adults.
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APA 7th
Trelle, A. N., Young, C. B., Vossler, H., Ramos Benitez, J., Cody, K. A., Mendiola, J. H., et al. (2025). Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14442
Vancouver
Trelle AN, Young CB, Vossler H, Ramos Benitez J, Cody KA, Mendiola JH, et al. Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.14442. PMID: 39713875.
BibTeX
@article{trelle2025-39713875,
author = {Trelle, A. N. and Young, C. B. and Vossler, H. and Ramos Benitez, J. and Cody, K. A. and Mendiola, J. H. and Swarovski, M. S. and Guen, Y. L. and others},
title = {{Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.14442},
pmid = {39713875},
url = {https://doi.org/10.1002/alz.14442}
}
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Key findings
- Results Plasma Aβ 42 /Aβ 40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955).
- Among SAMS CU, plasma Aβ 42 /Aβ 40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 59/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for 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 34 of the 58 points we could judge it on, which is 59 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 | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 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 | 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 39713875) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 34 of the 58 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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