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Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity
Alexis Moscoso, Fiona Heeman, Sheelakumari Raghavan, Alejandro Costoya‐Sánchez, Martijn van Essen, Ismini Mainta, Valle Camacho, Omar Darío Rodríguez-Fonseca et al.. JAMA, 2025-06-16
Topic: Brain proteins, microglia and lab models
Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET-positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET-positive/tau PET-negative (17% [95% CI, 13%-22%]) and Aβ PET-negative/tau PET-negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET-positive/tau PET-positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance: In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.
Key findings
- Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years.
- Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years.
- Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively).
- Most tau PET-positive individuals (92%) were also Aβ PET positive.
- Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET-positive/tau PET-negative (17% [95% CI, 13%-22%]) and Aβ PET-negative/tau PET-negative (6% [95% CI, 5%-8%]) individuals.
Why it matters
In 6,514 people, a positive tau PET scan was rare before age 50 but was estimated at 19% of cognitively unimpaired people by age 90, and at 79% of people with Alzheimer's dementia at age 75. Among cognitively unimpaired people, those positive on both amyloid and tau PET had an estimated 57% five-year risk of developing MCI or dementia, compared with 17% for amyloid-positive/tau-negative and 6% for people negative on both. The authors note this was a convenience sample and describe tau PET as a promising staging marker. These are associations, not a prediction for any one person.
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Study details
- Study designlongitudinal study
- Participants6,514
- Effect size50.5%; 9.8%
- Evidence strengthModerate
How this study scored 76/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 6,514 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 66 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 41.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 66 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Vasavan P. Nair: h-index 18 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 54 institution(s) in 10 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40522652) |
| Free to read | 2 / 2 | Free to read |
| Total | 76 / 100 | — |
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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., Heeman, F., Raghavan, S., Costoya‐Sánchez, A., van Essen, M., Mainta, I., et al. (2025). Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity. JAMA. https://doi.org/10.1001/jama.2025.7817
Vancouver
Moscoso A, Heeman F, Raghavan S, Costoya‐Sánchez A, van Essen M, Mainta I, et al. Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity. JAMA. 2025. doi:10.1001/jama.2025.7817. PMID: 40522652.
BibTeX
@article{moscoso2025-40522652,
author = {Moscoso, Alexis and Heeman, Fiona and Raghavan, Sheelakumari and Costoya‐Sánchez, Alejandro and van Essen, Martijn and Mainta, Ismini and Camacho, Valle and Rodríguez-Fonseca, Omar Darío and others},
title = {{Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity}},
journal = {JAMA},
year = {2025},
doi = {10.1001/jama.2025.7817},
pmid = {40522652},
url = {https://doi.org/10.1001/jama.2025.7817}
}
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