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Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum
de Leeuw DM, Trieu C, Vromen EM, Blujdea ER, Verberk IMW, Duits FH, Teunissen CE, Pijnenburg YAL et al.. JAMA network open, 2025-07-01
Topic: Amyloid, tau and blood-test diagnosis
Importance The trajectories of core Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers and the concurrent cognitive changes across the clinical spectrum remain unclear yet are important for clinical trial design. Objective To map longitudinal CSF amyloid, tau, and cognitive trajectories along the clinical spectrum of AD and amyloid-negative controls. Design, setting, and participants This longitudinal cohort study included participants with a minimum of 2 CSF samples from Alzheimer Centrum Amsterdam cohorts across the AD clinical spectrum (ie, abnormal amyloid levels at first visit, in different clinical stages) and cognitively normal controls with initially normal CSF markers from November 2003 to July 2019.
Key findings
- Objective To map longitudinal CSF amyloid, tau, and cognitive trajectories along the clinical spectrum of AD and amyloid-negative controls.
- Design, setting, and participants This longitudinal cohort study included participants with a minimum of 2 CSF samples from Alzheimer Centrum Amsterdam cohorts across the AD clinical spectrum (ie, abnormal amyloid levels at first visit, in different clinical stages) and cognitively normal controls with initially normal CSF markers from November 2003 to July 2019.
- The maximum follow-up period was 19.5 years (median [IQR], 2 [0-3] years).
- Data were analyzed from March 2024 to May 2025.
Why it matters
This long-term cohort study mapped how spinal fluid amyloid, tau, and cognitive measures change over time across the clinical spectrum of Alzheimer's disease. It is an observational study designed to inform clinical trial design, not to test a treatment or cure.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcohort study
- Participants197
- Effect size52.3%
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA network open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following 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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 197 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 12.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Betty Marije Tijms: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40638114) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2025.19919
- PubMed: 40638114
- Original source →
- Free full text: JAMA Network Open →
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
de Leeuw, D. M., Trieu, C., Vromen, E. M., Blujdea, E. R., Verberk, I. M. W., Duits, F. H., et al. (2025). Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum. JAMA network open. https://doi.org/10.1001/jamanetworkopen.2025.19919
Vancouver
de Leeuw DM, Trieu C, Vromen EM, Blujdea ER, Verberk IMW, Duits FH, et al. Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum. JAMA network open. 2025. doi:10.1001/jamanetworkopen.2025.19919. PMID: 40638114.
BibTeX
@article{deleeuw2025-40638114,
author = {de Leeuw, D. M. and Trieu, C. and Vromen, E. M. and Blujdea, E. R. and Verberk, I. M. W. and Duits, F. H. and Teunissen, C. E. and Pijnenburg, Y. A. L. and others},
title = {{Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum}},
journal = {JAMA network open},
year = {2025},
doi = {10.1001/jamanetworkopen.2025.19919},
pmid = {40638114},
url = {https://doi.org/10.1001/jamanetworkopen.2025.19919}
}
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