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A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease
Davina Biel, Anna Steward, Anna Dewenter, Amir Dehsarvi, Zeyu Zhu, Sebastian Niclas Roemer, Lukas K. Frontzkowski, Fabian Hirsch et al.. Alzheimer s & Dementia, 2025-10-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract INTRODUCTION With anti‐amyloid beta (Aβ) therapies approved for Alzheimer's disease (AD), surrogate biomarkers are needed to monitor clinical treatment efficacy. Therefore, we systematically compared longitudinal changes in A/T/N biomarkers (amyloid‐positron emission tomography [PET], tau‐PET, plasma phosphorylated tau at threonine 217 [p‐tau 217 ], and magnetic resonance imaging) for tracking cognitive changes. METHODS We analyzed longitudinal biomarker and cognitive change rates from the Alzheimer's Disease Neuroimaging Initiative ( N = 141) and Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) ( N = 151), estimated using linear mixed models. Using linear models, we tested biomarker changes as predictors of cognitive changes, comparing predictive strengths across biomarkers using bootstrapping. RESULTS Tau‐PET, plasma p‐tau217, and cortical thickness changes accurately tracked change rates in Mini‐Mental State Examination, Alzheimer's Disease Assessment Scale‐Cognitive Subscale 13‐item version, Clinical Dementia Rating‐Sum of Boxes, and Preclinial Alzheimer Cognitive Composite scores. In contrast, amyloid‐PET change rates were not linked to cognitive changes. DISCUSSION Plasma p‐tau 217 offers a cost‐effective AD‐specific alternative to tau‐PET and could potentially be implemented for monitoring cognitive changes in AD trials, while amyloid‐PET lacks utility. Cortical thickness changes accurately track cognitive changes but may be confounded by pseudo‐atrophy in anti‐Aβ treatments. Highlights Longitudinal changes in tau‐PET, plasma p‐tau 217 , cortical thickness – but not amyloid‐PET – effectively track cognitive decline. Cortical thickness may be confounded by pseudo‐atrophy in anti‐Aβ trials. Plasma p‐tau 217 is a robust and cost‐effective alternative to tau‐PET as an AD‐specific surrogate biomarker for monitoring cognitive changes.
Key findings
- RESULTS Tau‐PET, plasma p‐tau217, and cortical thickness changes accurately tracked change rates in Mini‐Mental State Examination, Alzheimer's Disease Assessment Scale‐Cognitive Subscale 13‐item version, Clinical Dementia Rating‐Sum of Boxes, and Preclinial Alzheimer Cognitive Composite scores.
Why it matters
Comparing different Alzheimer's biomarkers over time, this study found that tau-PET, plasma p-tau217 and cortical thickness changes tracked cognitive decline accurately, while amyloid-PET changes did not. The authors conclude that plasma p-tau217 offers a cost-effective, Alzheimer's-specific alternative to tau-PET that could potentially be used for monitoring.
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Study details
- Study designlongitudinal study
- Participants141
- Evidence strengthModerate
How this study scored 54/100
Published in a peer-reviewed 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. We have no data on senior author's track record, so that was left out: it earned 52 of the 96 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 141 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 | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41126448) |
| Free to read | 2 / 2 | Free to read |
| Points | 52 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 52 of the 96 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Biel, D., Steward, A., Dewenter, A., Dehsarvi, A., Zhu, Z., Roemer, S. N., et al. (2025). A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70783
Vancouver
Biel D, Steward A, Dewenter A, Dehsarvi A, Zhu Z, Roemer SN, et al. A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70783. PMID: 41126448.
BibTeX
@article{biel2025-41126448,
author = {Biel, Davina and Steward, Anna and Dewenter, Anna and Dehsarvi, Amir and Zhu, Zeyu and Roemer, Sebastian Niclas and Frontzkowski, Lukas K. and Hirsch, Fabian and others},
title = {{A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70783},
pmid = {41126448},
url = {https://doi.org/10.1002/alz.70783}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 25.