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Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Rodriguez JL, Snellman A, Suárez-Calvet M, Zetterberg H et al.. Brain : a journal of neurology, 2021-02-01
Topic: Amyloid, tau and blood-test diagnosis
Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer's disease. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer's disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer's disease.
Key findings
- Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology.
- Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment.
- Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer's disease.
- Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer's disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer's disease.
Why it matters
This study found that changes in blood p-tau181 occurred early and were associated with amyloid-beta pathology and with later widespread tau aggregation. It concerns a potential diagnostic and screening blood biomarker and does not test any treatment, cure, or prevention.
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Study details
- Study designprospective cohort
- Participants1,067
- Evidence strengthModerate
How this study scored 74/100
Published in a leading specialty journal, and it is a prospective cohort study, followed forward from enrollment. 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 71 of the 96 points we could judge it on, which is 74 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A prospective cohort study, followed forward from enrollment |
| 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 | 1,067 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 | 5 / 7 | Cited 231 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 22.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 29 other studies in this library |
| Still being cited | 3 / 4 | Cited 90 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) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33257949) |
| Free to read | 2 / 2 | Free to read |
| Points | 71 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 71 of the 96 points we could judge it on is 74 out of 100. |
| Total | 74 / 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
Moscoso, A., Grothe, M. J., Ashton, N. J., Karikari, T. K., Rodriguez, J. L., Snellman, A., et al. (2021). Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum. Brain : a journal of neurology. https://doi.org/10.1093/brain/awaa399
Vancouver
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Rodriguez JL, Snellman A, et al. Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum. Brain : a journal of neurology. 2021. doi:10.1093/brain/awaa399. PMID: 33257949.
BibTeX
@article{moscoso2021-33257949,
author = {Moscoso, A. and Grothe, M. J. and Ashton, N. J. and Karikari, T. K. and Rodriguez, J. L. and Snellman, A. and Suárez-Calvet, M. and Zetterberg, H. and others},
title = {{Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum}},
journal = {Brain : a journal of neurology},
year = {2021},
doi = {10.1093/brain/awaa399},
pmid = {33257949},
url = {https://doi.org/10.1093/brain/awaa399}
}
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