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Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex
Rik Ossenkoppele, Emma M Coomans, Liana G Apostolova, Suzanne L Baker, Henryk Barthel, Thomas G Beach, Tammy L S Benzinger, Tobey Betthauser et al.. Nature neuroscience, 2025-07-16
Topic: Plasma and spinal-fluid biomarkers
Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. APOE ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (N = 5,072 from 3 cohorts).
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APA 7th
Ossenkoppele, R., Coomans, E. M., Apostolova, L. G., Baker, S. L., Barthel, H., Beach, T. G., et al. (2025). Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex. Nature neuroscience. https://doi.org/10.1038/s41593-025-02000-6
Vancouver
Ossenkoppele R, Coomans EM, Apostolova LG, Baker SL, Barthel H, Beach TG, et al. Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex. Nature neuroscience. 2025. doi:10.1038/s41593-025-02000-6. PMID: 40670684.
BibTeX
@article{ossenkoppele2025-40670684,
author = {Ossenkoppele, Rik and Coomans, Emma M and Apostolova, Liana G and Baker, Suzanne L and Barthel, Henryk and Beach, Thomas G and Benzinger, Tammy L S and Betthauser, Tobey and others},
title = {{Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex}},
journal = {Nature neuroscience},
year = {2025},
doi = {10.1038/s41593-025-02000-6},
pmid = {40670684},
url = {https://doi.org/10.1038/s41593-025-02000-6}
}
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Key findings
- Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline.
- We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants.
- Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups.
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Study details
- Participants12,048
- Effect size1.1% to 4.4%; 17.4% to 22.2%; 68.0% to 52.9%
- Evidence strengthLow
How this study scored 63/100
Published in a leading specialty journal. Scored zero for study design and randomised / 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, multi-centre collaboration and free to read, so those were left out: it earned 35 of the 56 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 4 / 4 | 12,048 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40670684) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 35 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 35 of the 56 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
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