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Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment
Janelidze S, Barthélemy NR, Salvadó G, Schindler SE, Palmqvist S, Mattsson-Carlgren N, Braunstein JB, Ovod V, Bollinger JG, He Y, Li Y, Raji CA, et al.. JAMA Neurology, 2024-09-01
Topic: Brain proteins, microglia and lab models
Importance Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy in people with less severe disease. Plasma biomarkers will be essential for efficient screening of participants in future primary prevention clinical trials testing antiamyloid therapies in cognitively unimpaired (CU) individuals with initially low brain β-amyloid (Aβ) levels who are at high risk of accumulating Aβ. Objective To investigate if combining plasma biomarkers could be useful in predicting subsequent development of Aβ pathology in CU individuals with subthreshold brain Aβ levels (defined as Aβ levels Design, setting, and participants This was a longitudinal study including Swedish BioFINDER-2 (enrollment 2017-2022) and replication in 2 independent cohorts, the Knight Alzheimer Disease Research Center (Knight ADRC; enrollment 1988 and 2019) and Swedish BioFINDER-1 (enrollment 2009-2015). Included for analysis was a convenience sample of CU individuals with baseline plasma phosphorylated tau 217 (p-tau217) and Aβ42/40 assessments and Aβ assessments with positron emission tomography (Aβ-PET) or cerebrospinal fluid (CSF) Aβ42/40. Data were analyzed between April 2023 and May 2024. Exposures Baseline plasma levels of Aβ42/40, p-tau217, the ratio of p-tau217 to nonphosphorylated tau (%p-tau217), p-tau231, and glial fibrillary acidic protein (GFAP). Main outcomes and measures Cross-sectional and longitudinal PET and CSF measures of brain Aβ pathology. Results This study included 495 (BioFINDER-2), 283 (Knight ADRC), and 205 (BioFINDER-1) CU participants. In BioFINDER-2, the mean (SD) age was 65.7 (14.4) with 261 females (52.7%). When detecting abnormal CSF Aβ-status, a combination of plasma %p-tau217 and Aβ42/40 showed better performance (area under the curve = 0.949; 95% CI, 0.929-0.970; P Conclusions and relevance Results of this cohort study suggest that combining plasma p-tau217and Aβ42/40 levels could be useful for predicting development of Aβ pathology in people with early stages of subthreshold Aβ accumulation. These biomarkers might thus facilitate screening of participants for future primary prevention trials.
Key findings
- Importance Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy in people with less severe disease.
- Results This study included 495 (BioFINDER-2), 283 (Knight ADRC), and 205 (BioFINDER-1) CU participants.
- When detecting abnormal CSF Aβ-status, a combination of plasma %p-tau217 and Aβ42/40 showed better performance (area under the curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers.
Why it matters
In cognitively unimpaired people with initially low brain amyloid, combining plasma %p-tau217 and Aβ42/40 predicted subsequent amyloid accumulation better than either alone. This suggests blood biomarkers could help screen participants for primary prevention trials of antiamyloid therapies.
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Study details
- Study designcohort
- Participants983
- Effect sizeAUC 0.949 for CSF amyloid status with combined %p-tau217 and Aβ42/40
- Evidence strengthModerate
Limitations
BioFINDER and Knight ADRC cohorts are not fully representative of diverse populations; p-tau231 and GFAP were measured by immunoassays that may be less accurate than mass spectrometry; no longitudinal plasma data, so change over time could not be assessed as a predictor.
How this study scored 76/100
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. We have no data on free to read, so that was left out: it earned 74 of the 98 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 983 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 127 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 34.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 3 / 4 | Cited 127 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 | 3 / 3 | OpenAlex lists 13 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39068669) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 74 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 74 of the 98 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2024.2619
- PubMed: 39068669
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Janelidze, S., Barthélemy, N. R., Salvadó, G., Schindler, S. E., Palmqvist, S., Mattsson-Carlgren, N., et al. (2024). Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2024.2619
Vancouver
Janelidze S, Barthélemy NR, Salvadó G, Schindler SE, Palmqvist S, Mattsson-Carlgren N, et al. Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment. JAMA Neurology. 2024. doi:10.1001/jamaneurol.2024.2619. PMID: 39068669.
BibTeX
@article{janelidze2024-39068669,
author = {Janelidze, S. and Barthélemy, N. R. and Salvadó, G. and Schindler, S. E. and Palmqvist, S. and Mattsson-Carlgren, N. and Braunstein, J. B. and Ovod, V. and Bollinger, J. G. and He, Y. and Li, Y. and Raji, C. A. and others},
title = {{Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment}},
journal = {JAMA Neurology},
year = {2024},
doi = {10.1001/jamaneurol.2024.2619},
pmid = {39068669},
url = {https://doi.org/10.1001/jamaneurol.2024.2619}
}
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