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Tau from SPAM Transgenic Mice Exhibit Potent Strain-Specific Prion-Like Seeding Properties Characteristic of Human Neurodegenerative Diseases
Ethan D. Smith, Giavanna Paterno, Brach M. Bell, Kimberly-Marie M. Gorion, Stefan Prokop, Benoit I. Giasson. NeuroMolecular Medicine, 2025-05-30
Topic: Brain proteins, microglia and lab models
Tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), are characterized by the aberrant aggregation of tau protein into neurofibrillary tangles. Despite extensive studies on tau aggregation, the mechanisms of tau misfolding and propagation remain incompletely understood. In this study, we utilize the SPAM (S320F/P301S) tau transgenic mouse model, which expresses 0N4R human tau with two FTDP-17 mutations, to investigate the biochemical properties and seeding potential of misfolded tau from these mice. Sarkosyl extraction and ultracentrifugation were employed to isolate detergent-insoluble tau aggregates (SPAM-tau) from aged SPAM mice. These aggregates were then tested for their prion-type seeding activity in an established HEK293T cell model comparing the induced aggregation of wild-type and mutant forms of human and murine tau. Our results show that SPAM-tau exhibits distinct and vigorous prion-like seeding properties, inducing the aggregation of human and murine tau homologues with the formation of amyloidogenic (Thioflavin S-positive) inclusions. Importantly, SPAM-tau aggregates can facilitate the prion-type misfolding of wild-type and mutant forms of human and mouse tau. We demonstrated that these induced tau aggregates are able to be further transmitted in passaging studies. Furthermore, SPAM-tau preferentially templated 4R tau isoforms, sharing strain-like seeding properties with insoluble tau derived from the brains of individuals with progressive supranuclear palsy (PSP-tau). In summary, these findings enhance our understanding of tau aggregation and propagation, suggesting that SPAM-tau may serve as a valuable tool for studying tauopathies and evaluating potential therapeutic strategies aimed at halting tau misfolding and propagation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Smith, E. D., Paterno, G., Bell, B. M., Gorion, K.-M. M., Prokop, S., & Giasson, B. I. (2025). Tau from SPAM Transgenic Mice Exhibit Potent Strain-Specific Prion-Like Seeding Properties Characteristic of Human Neurodegenerative Diseases. NeuroMolecular Medicine. https://doi.org/10.1007/s12017-025-08850-4
Vancouver
Smith ED, Paterno G, Bell BM, Gorion K.-MM, Prokop S, Giasson BI. Tau from SPAM Transgenic Mice Exhibit Potent Strain-Specific Prion-Like Seeding Properties Characteristic of Human Neurodegenerative Diseases. NeuroMolecular Medicine. 2025. doi:10.1007/s12017-025-08850-4. PMID: 40447946.
BibTeX
@article{smith2025-40447946,
author = {Smith, Ethan D. and Paterno, Giavanna and Bell, Brach M. and Gorion, Kimberly-Marie M. and Prokop, Stefan and Giasson, Benoit I.},
title = {{Tau from SPAM Transgenic Mice Exhibit Potent Strain-Specific Prion-Like Seeding Properties Characteristic of Human Neurodegenerative Diseases}},
journal = {NeuroMolecular Medicine},
year = {2025},
doi = {10.1007/s12017-025-08850-4},
pmid = {40447946},
url = {https://doi.org/10.1007/s12017-025-08850-4}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Our results show that SPAM-tau exhibits distinct and vigorous prion-like seeding properties, inducing the aggregation of human and murine tau homologues with the formation of amyloidogenic (Thioflavin S-positive) inclusions.
- We demonstrated that these induced tau aggregates are able to be further transmitted in passaging studies.
- In summary, these findings enhance our understanding of tau aggregation and propagation, suggesting that SPAM-tau may serve as a valuable tool for studying tauopathies and evaluating potential therapeutic strategies aimed at halting tau misfolding and propagation.
Why it matters
In mice engineered to carry human tau with two FTDP-17 mutations, the extracted tau aggregates could force normal human and mouse tau to clump and these clumps could be passed on in lab studies. This is early animal and cell work, so it does not yet show a way to treat or prevent Alzheimer's in people.
Study details
- Evidence strengthLow
How this study scored 37/100
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 (NeuroMolecular Medicine) |
| Journal's citation record | 1 / 4 | NeuroMolecular Medicine: journal h-index 100 (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 “transgenic”) — 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 | 3 / 4 | Last-listed author Benoit I. Giasson: h-index 87 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Florida: institution h-index 1,303 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40447946) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s12017-025-08850-4
- PubMed: 40447946
- Original source →
- Free full text: NeuroMolecular 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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