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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring
Nicholas James Ashton, Shorena Janelidze, Niklas Mattsson, Alexa Pichet Binette, Olof T. Strandberg, Wagner Scheeren Brum, Thomas K. Karikari, Fernando González‐Ortiz, Guglielmo Di Molfetta, Francisco J. Meda, Erin McMullen Jonaitis, Rebecca L. Koscik, Karly Alex Cody, Tobey J. Betthauser, Yan Li, Eugeen Vanmechelen, Sebastian Palmqvist, Erik Stomrud, Randall John Bateman, Henrik Zetterberg, Sterling C. Johnson, Kaj Blennow, Oskar Hansson. Nature Medicine, 2022-12-01
Topic: Amyloid, tau and blood-test diagnosis
Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.
Why it matters
In the BioFINDER-1 cohort, blood p-tau231 and the amyloid-beta 42/40 ratio were more changed at lower levels of amyloid pathology, but only p-tau217 rose markedly over 4-6 years and its increases were associated with cognitive decline and brain atrophy. This was confirmed in a second cohort, and the authors highlight p-tau217 as a marker of disease progression in preclinical and prodromal Alzheimer's disease.
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How this study scored 64/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on strength of evidence, so that was left out: it earned 61 of the 95 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 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 | 6 / 7 | Cited 433 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 72.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 6 / 6 | Cited 43.9× 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 | 4 / 4 | Cited 358 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 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36456833) |
| Free to read | 2 / 2 | Free to read |
| Points | 61 / 95 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 61 of the 95 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-022-02074-w
- PubMed: 36456833
- Original source →
- Free full text: Nature Medicine →
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 names 23 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Ashton, N. J., Janelidze, S., Mattsson, N., Binette, A. P., Strandberg, O. T., Brum, W. S., et al. (2022). Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nature Medicine. https://doi.org/10.1038/s41591-022-02074-w
Vancouver
Ashton NJ, Janelidze S, Mattsson N, Binette AP, Strandberg OT, Brum WS, et al. Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nature Medicine. 2022. doi:10.1038/s41591-022-02074-w. PMID: 36456833.
BibTeX
@article{ashton2022-36456833,
author = {Ashton, Nicholas James and Janelidze, Shorena and Mattsson, Niklas and Binette, Alexa Pichet and Strandberg, Olof T. and Brum, Wagner Scheeren and Karikari, Thomas K. and González‐Ortiz, Fernando and Di Molfetta, Guglielmo and Meda, Francisco J. and Jonaitis, Erin McMullen and Koscik, Rebecca L. and Cody, Karly Alex and Betthauser, Tobey J. and Li, Yan and Vanmechelen, Eugeen and Palmqvist, Sebastian and Stomrud, Erik and Bateman, Randall John and Zetterberg, Henrik and Johnson, Sterling C. and Blennow, Kaj and Hansson, Oskar},
title = {{Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring}},
journal = {Nature Medicine},
year = {2022},
doi = {10.1038/s41591-022-02074-w},
pmid = {36456833},
url = {https://doi.org/10.1038/s41591-022-02074-w}
}
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