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Seeding biosensor cell line that reproduces the Alzheimer tau fold
Panagiotis Katsinelos, Sofia Lövestam, Chao Qi, Benjamin Falcon, Jennifer A. Macdonald, Gabriel Stephenson, Bernardino Francesco Ghetti, Ann Carolyn McKee et al.. Journal of Biological Chemistry, 2025-11-20
Topic: Amyloid, tau and blood-test diagnosis
The assembly of tau protein into amyloid filaments through templated seeding is believed to underlie the propagation of pathology in neurodegenerative diseases, such as Alzheimer's disease (AD) and other tauopathies. A commonly used model system for studying this process is through the induction of tau filament formation in cultured cells following the addition of tau seeds isolated from the human brain. However, little is known about the structures of seeded filaments; some biosensor cell lines are unable to reproduce the tau filament structures from AD, because they overexpress tau fragments that do not cover the whole of the ordered filament core. Here, we describe a novel tau seeding biosensor model in human embryonic kidney 293T cells that overexpress residues K297-E391 of human 4R tau. The construct contains an N-terminal hemagglutinin tag, which allows the specific detection of the amplified template. The biosensor cells detected filaments seeded by material from sporadic three-repeat (3R) + four-repeat (4R) tauopathies, with little activity by seeds from 3R-only or 4R-only tauopathies. The sensitivity of seed detection from 3R + 4R tauopathies in our system was similar to or higher than for previously reported biosensors. We also structurally characterized the AD-seeded tau filaments by cryo-EM. Most of the cell-derived filaments consisted of two protofilaments with the Alzheimer's fold but with a "head-to-head" interprotofilament packing. Our results establish a sensitive biosensor cell line with specificity toward seeds from 3R + 4R tauopathies.
Key findings
- Our results establish a sensitive biosensor cell line with specificity toward seeds from 3R + 4R tauopathies.
Why it matters
The researchers created a new lab cell line that detects tau seeds from 3R + 4R tauopathies, including Alzheimer's disease, with sensitivity similar to or higher than earlier biosensors. This is a laboratory tool for studying and detecting tau, not a treatment, cure or prevention for patients.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Biological Chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “cell line”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Michel Goedert: h-index 147 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Boston University: institution h-index 1,456 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41260337) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.jbc.2025.110952
- PubMed: 41260337
- Original source →
- Free full text: Journal of Biological Chemistry →
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
Katsinelos, P., Lövestam, S., Qi, C., Falcon, B., Macdonald, J. A., Stephenson, G., et al. (2025). Seeding biosensor cell line that reproduces the Alzheimer tau fold. Journal of Biological Chemistry. https://doi.org/10.1016/j.jbc.2025.110952
Vancouver
Katsinelos P, Lövestam S, Qi C, Falcon B, Macdonald JA, Stephenson G, et al. Seeding biosensor cell line that reproduces the Alzheimer tau fold. Journal of Biological Chemistry. 2025. doi:10.1016/j.jbc.2025.110952. PMID: 41260337.
BibTeX
@article{katsinelos2025-41260337,
author = {Katsinelos, Panagiotis and Lövestam, Sofia and Qi, Chao and Falcon, Benjamin and Macdonald, Jennifer A. and Stephenson, Gabriel and Ghetti, Bernardino Francesco and McKee, Ann Carolyn and others},
title = {{Seeding biosensor cell line that reproduces the Alzheimer tau fold}},
journal = {Journal of Biological Chemistry},
year = {2025},
doi = {10.1016/j.jbc.2025.110952},
pmid = {41260337},
url = {https://doi.org/10.1016/j.jbc.2025.110952}
}
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