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Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics
Bluma M, Chiotis K, Bucci M, Savitcheva I, Matton A, Kivipelto M, Jeromin A, De Santis G et al.. EBioMedicine, 2024-12-18
Topic: Amyloid, tau and blood-test diagnosis
Background Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers. Methods In a memory clinic cohort, we analysed plasma pTau181, pTau217, pTau231, respectively, GFAP, NfL, CSF pTau181, Aβ-PET scans, and MRI/CT visual read of atrophy. We utilized methods based on multiple linear regression to evaluate the specific associations between clinically used and recently developed plasma biomarkers, while also considering demographic variables such as age and sex. Findings Although plasma pTau181, pTau217, pTau231, and GFAP were significantly associated with both Aβ-PET and CSF pTau181, Aβ-PET explained more variance in the levels of these biomarkers. The effect of CSF pTau181 on plasma GFAP and pTau181 was completely attenuated by Aβ-PET, whereas pTau231 and pTau217 were affected by both Aβ-PET and CSF pTau181 levels. Unlike these biomarkers, increased NfL was rather indicative of brain atrophy and older age. Based on the effect sizes, plasma pTau217 emerged as highly effective in distinguishing between A+ and A-, and T+ and T- individuals, with 60% of variance in plasma pTau217 explained by clinical AD biomarkers. Interpretation Amyloid burden primarily drives the changes in plasma pTau181, pTau217, pTau231, and GFAP. In contrast to plasma pTau217, a significant portion of variance in plasma pTau181, pTau231, GFAP, NfL remains unexplained by clinical AD biomarkers. Funding This research is supported by the Swedish Research Council VR: 2017-06086, 2020-4-3018, 2024-2027; Swedish Brain Foundation, Swedish Alzhzeimer Foundation, CIMED Region Stockholm/Karolinska Institutet; the Region Stockholm - Karolinska Institutet regional agreement on medical training and clinical research (ALF), Fondation Recherche sur Alzheimer (France).
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APA 7th
Bluma, M., Chiotis, K., Bucci, M., Savitcheva, I., Matton, A., Kivipelto, M., et al. (2025). Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics. EBioMedicine. https://doi.org/10.1016/j.ebiom.2024.105504
Vancouver
Bluma M, Chiotis K, Bucci M, Savitcheva I, Matton A, Kivipelto M, et al. Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics. EBioMedicine. 2025. doi:10.1016/j.ebiom.2024.105504. PMID: 39701863.
BibTeX
@article{bluma2025-39701863,
author = {Bluma, M. and Chiotis, K. and Bucci, M. and Savitcheva, I. and Matton, A. and Kivipelto, M. and Jeromin, A. and De Santis, G. and others},
title = {{Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics}},
journal = {EBioMedicine},
year = {2025},
doi = {10.1016/j.ebiom.2024.105504},
pmid = {39701863},
url = {https://doi.org/10.1016/j.ebiom.2024.105504}
}
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Key findings
- Background Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness.
- Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD.
- Findings Although plasma pTau181, pTau217, pTau231, and GFAP were significantly associated with both Aβ-PET and CSF pTau181, Aβ-PET explained more variance in the levels of these biomarkers.
- In contrast to plasma pTau217, a significant portion of variance in plasma pTau181, pTau231, GFAP, NfL remains unexplained by clinical AD biomarkers.
Why it matters
In this memory clinic cohort, several plasma biomarkers were associated with amyloid PET and CSF p-tau181, with amyloid PET explaining more of the variance, and plasma pTau217 was highly effective at distinguishing amyloid-positive from amyloid-negative and tau-positive from tau-negative individuals. This is a biomarker comparison study and does not show that using these markers changes treatment outcomes.
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Study details
- Evidence strengthModerate
How this study scored 50/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EBioMedicine) |
| Journal's citation record | 2 / 4 | EBioMedicine: journal h-index 181 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 3 / 7 | Cited 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.1× 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 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Agneta K. Nordberg: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39701863) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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