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Disease staging of Alzheimer's disease using a CSF-based biomarker model
Salvadó G, Horie K, Barthélemy NR, Vogel JW, Pichet Binette A, Chen CD, Aschenbrenner AJ, Gordon BA et al.. Nature aging, 2024-03-21
Topic: Amyloid, tau and blood-test diagnosis
Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The CSF stages (0-5) demonstrated a correlation with increased abnormalities in other AD-related biomarkers, such as Aβ-PET and tau-PET, and aligned with longitudinal biomarker changes reflective of AD progression. Higher CSF stages at baseline were associated with an elevated hazard ratio of clinical decline. This study highlights a common molecular pathway underlying AD pathophysiology across all patients, suggesting that a single CSF collection can accurately indicate the presence of AD pathologies and characterize the stage of disease progression. The proposed staging model has implications for enhancing diagnostic and prognostic assessments in both clinical practice and the design of clinical trials.
Key findings
- SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau).
- The CSF stages (0-5) demonstrated a correlation with increased abnormalities in other AD-related biomarkers, such as Aβ-PET and tau-PET, and aligned with longitudinal biomarker changes reflective of AD progression.
- Higher CSF stages at baseline were associated with an elevated hazard ratio of clinical decline.
- This study highlights a common molecular pathway underlying AD pathophysiology across all patients, suggesting that a single CSF collection can accurately indicate the presence of AD pathologies and characterize the stage of disease progression.
Why it matters
This study used five cerebrospinal fluid biomarkers to build a staging model (stages 0-5) that tracked with other Alzheimer's biomarkers and predicted clinical decline. It suggests a single spinal fluid collection may help identify and stage Alzheimer's pathology, which could improve diagnosis and prognosis, though it is a biomarker model rather than a treatment.
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Study details
- Study designlongitudinal study
- Participants426
- Evidence strengthModerate
How this study scored 69/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 426 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 116 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 29.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 31.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 116 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38514824) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Salvadó, G., Horie, K., Barthélemy, N. R., Vogel, J. W., Pichet Binette, A., Chen, C. D., et al. (2024). Disease staging of Alzheimer's disease using a CSF-based biomarker model. Nature aging. https://doi.org/10.1038/s43587-024-00599-y
Vancouver
Salvadó G, Horie K, Barthélemy NR, Vogel JW, Pichet Binette A, Chen CD, et al. Disease staging of Alzheimer's disease using a CSF-based biomarker model. Nature aging. 2024. doi:10.1038/s43587-024-00599-y. PMID: 38514824.
BibTeX
@article{salvado2024-38514824,
author = {Salvadó, G. and Horie, K. and Barthélemy, N. R. and Vogel, J. W. and Pichet Binette, A. and Chen, C. D. and Aschenbrenner, A. J. and Gordon, B. A. and others},
title = {{Disease staging of Alzheimer's disease using a CSF-based biomarker model}},
journal = {Nature aging},
year = {2024},
doi = {10.1038/s43587-024-00599-y},
pmid = {38514824},
url = {https://doi.org/10.1038/s43587-024-00599-y}
}
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