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An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration
Madison I. J. Honey, Yanaika Sylvana Hok-A-Hin, Elisabeth H. Thijssen, Katheryn A Q Cousins, Babette van der Weijden, Lisanne in ‘t Veld, Erik Stoops, Sterre C.M. de Boer et al.. Nature Medicine, 2026-04-15
Topic: Brain proteins, microglia and lab models
Biomarkers to determine underlying frontotemporal lobar degeneration (FTLD) tau or TAR DNA-binding protein (TDP) pathology during life are needed to advance clinical trials targeting specific FTD pathologies. For this purpose, we developed a new ultrasensitive immunoassay to quantify acetylated tau at lysine 174 (AcTau174) in cerebrospinal fluid (CSF). In a sporadic cohort (n = 513), AcTau174 concentrations were higher in all dementia groups (FTLD-TDP, FTLD-Tau, Alzheimer's disease (AD), mild cognitive impairment (MCI)-AD and dementia with Lewy bodies (DLB)) compared to controls. The largest increase was observed in the FTLD-TDP group, particularly patients with semantic variant primary progressive aphasia (svPPA) and GRN mutation carriers. Notably, AcTau174 discriminated FTLD-TDP from FTLD-Tau (area under the curve (AUC) = 0.83, 95% confidence interval (CI) = 0.75-0.91) and FTLD-TDP from controls (AUC = 0.95, 95% CI = 0.92-0.99) with high accuracy. This was replicated in independent, sporadic and genetic validation cohorts (164 patients and 24 controls), albeit with somewhat lower accuracy (FTLD-TDP versus FTLD-Tau; AUC range = 0.75-0.79) and wider CIs. Within the FTLD-TDP, AD and MCI-AD groups, higher AcTau174 concentrations were associated with a faster cognitive decline over time. In summary, CSF AcTau174 has great potential to discriminate FTLD-TDP from FTLD-Tau as a biomarker reflecting FTLD-TDP disease severity and progression.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Honey, M. I. J., Hok-A-Hin, Y. S., Thijssen, E. H., Cousins, K. A. Q., van der Weijden, B., Veld, L. i. ‘., et al. (2026). An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration. Nature Medicine. https://doi.org/10.1038/s41591-026-04341-6
Vancouver
Honey MIJ, Hok-A-Hin YS, Thijssen EH, Cousins KAQ, van der Weijden B, Veld Li‘, et al. An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration. Nature Medicine. 2026. doi:10.1038/s41591-026-04341-6. PMID: 41986736.
BibTeX
@article{honey2026-41986736,
author = {Honey, Madison I. J. and Hok-A-Hin, Yanaika Sylvana and Thijssen, Elisabeth H. and Cousins, Katheryn A Q and van der Weijden, Babette and Veld, Lisanne in ‘t and Stoops, Erik and de Boer, Sterre C.M. and others},
title = {{An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration}},
journal = {Nature Medicine},
year = {2026},
doi = {10.1038/s41591-026-04341-6},
pmid = {41986736},
url = {https://doi.org/10.1038/s41591-026-04341-6}
}
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.
Key findings
- In a sporadic cohort (n = 513), AcTau174 concentrations were higher in all dementia groups (FTLD-TDP, FTLD-Tau, Alzheimer's disease (AD), mild cognitive impairment (MCI)-AD and dementia with Lewy bodies (DLB)) compared to controls.
- This was replicated in independent, sporadic and genetic validation cohorts (164 patients and 24 controls), albeit with somewhat lower accuracy (FTLD-TDP versus FTLD-Tau; AUC range = 0.75-0.79) and wider CIs.
- Within the FTLD-TDP, AD and MCI-AD groups, higher AcTau174 concentrations were associated with a faster cognitive decline over time.
Why it matters
A new immunoassay measuring acetylated tau at lysine 174 in cerebrospinal fluid was higher in all dementia groups than in controls, with the largest increase in FTLD-TDP, and it distinguished FTLD-TDP from FTLD-Tau with high accuracy in the main cohort. Higher levels were also associated with faster cognitive decline in some groups, suggesting potential as a biomarker to tell these pathologies apart.
Study details
- Participants513
- Effect sizeAUC = 0.95
- Evidence strengthModerate
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design and randomized / 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 513 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 20.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Charlotte Elisabeth Teunissen: h-index 116 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41986736) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-026-04341-6
- PubMed: 41986736
- 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).
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