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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, Rodriguez JL, Snellman A, Suárez-Calvet M, Chaudhuri PS, Lussier F et al.. Molecular psychiatry, 2020-07-16
Topic: Amyloid, tau and blood-test diagnosis
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 >1,000 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 did not show increased plasma p-tau181. 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.
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APA 7th
Karikari, T. K., Benedet, A. L., Ashton, N. J., Rodriguez, J. L., Snellman, A., Suárez-Calvet, M., et al. (2020). Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Molecular psychiatry. https://doi.org/10.1101/2020.07.15.20154237
Vancouver
Karikari TK, Benedet AL, Ashton NJ, Rodriguez JL, 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. 2020. doi:10.1101/2020.07.15.20154237.
BibTeX
@article{karikari2020-01fa071e,
author = {Karikari, T. K. and Benedet, A. L. and Ashton, N. J. and Rodriguez, J. L. and Snellman, A. and Suárez-Calvet, M. and Chaudhuri, P. S. 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 = {2020},
doi = {10.1101/2020.07.15.20154237},
url = {https://doi.org/10.1101/2020.07.15.20154237}
}
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.
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Study details
- Study designlongitudinal study
- Participants1,000
- Effect sizeAUC=85.3; 81.4%; 89.2%
- Evidence strengthModerate
How this study scored 72/100
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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 42 of the 58 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 5 | 2020 — within 10 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33106600) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 42 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 42 of the 58 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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