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Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community
Giulia Grande, Martina Valletta, Debora Rizzuto, Xin Rui Xia, Chengxuan Qiu, Nicola Orsini, Matilda Dale, Sarah Wamala Andersson et al.. Nature Medicine, 2025-03-26
Topic: Amyloid, tau and blood-test diagnosis
Evidence regarding the clinical validity of blood biomarkers of Alzheimer's disease (AD) in the general population is limited. We estimated the hazard and predictive performance of six AD blood biomarkers for incident all-cause and AD dementia-the ratio of amyloid-β 42 to amyloid-β 40 and levels of tau phosphorylated at T217 (p-tau217), tau phosphorylated at T181 (p-tau181), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-in a cohort of 2,148 dementia-free older adults from Sweden, who were followed for up to 16 years. In multi-adjusted Cox regression models, elevated baseline levels of p-tau181, p-tau217, NfL, and GFAP were associated with a significantly increased hazard for all-cause and AD dementia, displaying a non-linear dose-response relationship. Elevated concentrations of p-tau181, p-tau217, NfL, and GFAP demonstrated strong predictive performance (area under the curve ranging from 70.9% to 82.6%) for 10-year all-cause and AD dementia, with negative predictive values exceeding 90% but low positive predictive values (PPVs). Combining p-tau217 with NfL or GFAP further improved prediction, with PPVs reaching 43%. Our findings suggest that these biomarkers have the potential to rule out impending dementia in community settings, but they might need to be combined with other biological or clinical markers to be used as screening tools.
Key findings
- In multi-adjusted Cox regression models, elevated baseline levels of p-tau181, p-tau217, NfL, and GFAP were associated with a significantly increased hazard for all-cause and AD dementia, displaying a non-linear dose-response relationship.
- Elevated concentrations of p-tau181, p-tau217, NfL, and GFAP demonstrated strong predictive performance (area under the curve ranging from 70.9% to 82.6%) for 10-year all-cause and AD dementia, with negative predictive values exceeding 90% but low positive predictive values (PPVs).
- Our findings suggest that these biomarkers have the potential to rule out impending dementia in community settings, but they might need to be combined with other biological or clinical markers to be used as screening tools.
Why it matters
In 2,148 dementia-free older adults in Sweden followed for up to 16 years, higher blood levels of p-tau181, p-tau217, NfL and GFAP were linked to higher risk of all-cause and Alzheimer's dementia. Over 10 years, a negative result was reassuring (negative predictive value above 90%), but a positive one was not: even the best pairing, p-tau217 with NfL or GFAP, had a positive predictive value of only 43%. The authors conclude that these tests may help rule out impending dementia, but probably need to be combined with other biological or clinical markers before they can be used for screening.
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Study details
- Effect size70.9% to 82.6%
- Evidence strengthModerate
How this study scored 65/100
Published in a top-tier journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 170 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 56.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 108.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 170 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Davide Liborio Vetrano: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40140622) |
| Free to read | 2 / 2 | Free to read |
| Total | 65 / 100 | — |
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Read the original
- DOI: 10.1038/s41591-025-03605-x
- PubMed: 40140622
- Original source →
- Free full text: Nature Medicine →
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
Grande, G., Valletta, M., Rizzuto, D., Xia, X. R., Qiu, C., Orsini, N., et al. (2025). Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community. Nature Medicine. https://doi.org/10.1038/s41591-025-03605-x
Vancouver
Grande G, Valletta M, Rizzuto D, Xia XR, Qiu C, Orsini N, et al. Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community. Nature Medicine. 2025. doi:10.1038/s41591-025-03605-x. PMID: 40140622.
BibTeX
@article{grande2025-40140622,
author = {Grande, Giulia and Valletta, Martina and Rizzuto, Debora and Xia, Xin Rui and Qiu, Chengxuan and Orsini, Nicola and Dale, Matilda and Andersson, Sarah Wamala and others},
title = {{Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community}},
journal = {Nature Medicine},
year = {2025},
doi = {10.1038/s41591-025-03605-x},
pmid = {40140622},
url = {https://doi.org/10.1038/s41591-025-03605-x}
}
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