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Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease
Chen SD, Huang YY, Shen XN, Guo Y, Tan L, Dong Q, Yu JT, Alzheimer’s Disease Neuroimaging Initiative.. Translational psychiatry, 2021-06-12
Topic: Amyloid, tau and blood-test diagnosis
To assess plasma phosphorylated tau181 (p-tau181) as a progression biomarker in Alzheimer's disease (AD), we examined longitudinal plasma p-tau181 of 1184 participants (403 cognitively normal (CN), 560 patients with mild cognitive impairment (MCI), and 221 with AD dementia) from Alzheimer's Disease Neuroimaging Initiative (ADNI). The plasma p-tau level was increased at baseline for MCI and AD dementia (mean: CN, 15.4 pg/mL; MCI, 18.4 pg/mL; AD dementia, 23.7 pg/mL; P < 0.001) and increased significantly over time at preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stage of AD. A longitudinal increase of plasma p-tau181 was associated with abnormal cerebrospinal fluid biomarker levels (low Aβ42, high phosphorylated tau, and high total tau, all P < 0.001), amyloid accumulation (P < 0.001) and hypometabolism (P = 0.002) on positron emission tomo
Key findings
- The plasma p-tau level was increased at baseline for MCI and AD dementia (mean: CN, 15.4 pg/mL; MCI, 18.4 pg/mL; AD dementia, 23.7 pg/mL; P < 0.001) and increased significantly over time at preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stage of AD.
- A longitudinal increase of plasma p-tau181 was associated with abnormal cerebrospinal fluid biomarker levels (low Aβ42, high phosphorylated tau, and high total tau, all P < 0.001), amyloid accumulation (P < 0.001) and hypometabolism (P = 0.002) on positron emission tomography, atrophy in structure imaging (small hippocampal (P = 0.030), middle temporal (P = 0.008), and whole brain (P = 0.027) volume, and large ventricular volume (P = 0.008)), and deteriorated cognitive performance (global cognition and memory, language, executive function, and visuospatial function, all P < 0.050) at baseline.
- Furthermore, longitudinal plasma p-tau181 correlated with concurrent changes of nearly all these AD-related hallmarks and faster increase in plasma p-tau181 correlated with faster worsening cognition in all diagnostic groups.
- Importantly, most associations remained significant in Aβ-positive group and became non-significant in Aβ-negative group.
Why it matters
In 1,184 participants, plasma phosphorylated tau 181 was higher at baseline in those with mild cognitive impairment and Alzheimer's dementia and increased over time across preclinical, prodromal, and dementia stages. This marker was also linked to abnormal cerebrospinal fluid biomarkers, amyloid accumulation, and hypometabolism on PET scans, suggesting it may help track disease progression.
Study details
- Study designlongitudinal study
- Participants1,184
- Evidence strengthModerate
How this study scored 60/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. 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 58 of the 96 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational psychiatry) |
| Journal's citation record | 2 / 4 | Translational Psychiatry: journal h-index 180 (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 | 1,184 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 | 4 / 7 | Cited 64 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 6.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 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 | 1 / 3 | Fudan University: institution h-index 954 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34120152) |
| Free to read | 2 / 2 | Free to read |
| Points | 58 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 58 of the 96 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41398-021-01476-7
- PubMed: 34120152
- Original source →
- Free full text: Translational Psychiatry →
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 8 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
Chen, S. D., Huang, Y. Y., Shen, X. N., Guo, Y., Tan, L., Dong, Q., et al. (2021). Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease. Translational psychiatry. https://doi.org/10.1038/s41398-021-01476-7
Vancouver
Chen SD, Huang YY, Shen XN, Guo Y, Tan L, Dong Q, et al. Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease. Translational psychiatry. 2021. doi:10.1038/s41398-021-01476-7. PMID: 34120152.
BibTeX
@article{chen2021-34120152,
author = {Chen, S. D. and Huang, Y. Y. and Shen, X. N. and Guo, Y. and Tan, L. and Dong, Q. and Yu, J. T. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease}},
journal = {Translational psychiatry},
year = {2021},
doi = {10.1038/s41398-021-01476-7},
pmid = {34120152},
url = {https://doi.org/10.1038/s41398-021-01476-7}
}
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