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Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative
Karikari TK, Benedet AL, Ashton NJ, Lantero Rodriguez J, Snellman A, Suárez-Calvet M, Saha-Chaudhuri P, Lussier F et al.. Molecular psychiatry, 2020-10-26
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study of 1,000 participants. In more than 1000 people from the Alzheimer's Disease Neuroimaging Initiative, blood p-tau181 was already raised before symptoms in people with amyloid on PET and rose further in mild cognitive impairment and Alzheimer's dementia. Reported effect size: AUC = 85.3; 89.2%; AUC = 76.9.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Karikari, T. K., Benedet, A. L., Ashton, N. J., Lantero Rodriguez, J., Snellman, A., Suárez-Calvet, M., et al. (2021). Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative. Molecular psychiatry. https://doi.org/10.1038/s41380-020-00923-z
Vancouver
Karikari TK, Benedet AL, Ashton NJ, Lantero Rodriguez J, Snellman A, Suárez-Calvet M, et al. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative. Molecular psychiatry. 2021. doi:10.1038/s41380-020-00923-z. PMID: 33106600.
BibTeX
@article{karikari2021-33106600,
author = {Karikari, T. K. and Benedet, A. L. and Ashton, N. J. and Lantero Rodriguez, J. and Snellman, A. and Suárez-Calvet, M. and Saha-Chaudhuri, P. and Lussier, F. and others},
title = {{Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative}},
journal = {Molecular psychiatry},
year = {2021},
doi = {10.1038/s41380-020-00923-z},
pmid = {33106600},
url = {https://doi.org/10.1038/s41380-020-00923-z}
}
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.
Key findings
- Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%).
- Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target.
- This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.
Why it matters
In more than 1000 people from the Alzheimer's Disease Neuroimaging Initiative, blood p-tau181 was already raised before symptoms in people with amyloid on PET and rose further in mild cognitive impairment and Alzheimer's dementia. It separated Alzheimer's dementia well (AUC 85.3%) but amyloid-positive from amyloid-negative people less well (AUC 76.9%), and higher baseline levels predicted later dementia about as well as the spinal-fluid p-tau181 test. These are group-level results from a research cohort with no stated cut-off, so they do not show that one blood result can diagnose or forecast Alzheimer's in an individual.
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Study details
- Study designlongitudinal study
- Participants1,000
- Effect sizeAUC = 85.3; 89.2%; AUC = 76.9
- Evidence strengthModerate
How this study scored 76/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomized / 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 73 of the 96 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,000 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 349 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 49.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 33.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 37 other studies in this library |
| Still being cited | 3 / 4 | Cited 139 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 | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 21 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33106600) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 73 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 73 of the 96 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 →
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