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Development of small molecules promoting tau degradation in Alzheimer disease
Bengt Winblad, Lisha Wang, Banesh Sooram, Thomai Mouskeftara, Rajnish Kumar, Sophia Schedin Weiss, Lars O. Tjernberg. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Within around 700 new designed PROTACs, we found by computational modelling more than 25 PROTACs that were predicted to have a better ability to form ternary complexes than the previously reported PROTACs. Pharmacokinetic predictions suggested that several PROTACs should have good oral bioavailability, brain permeability and low toxicity. Some of the selected PROTACs showed good stability during molecular dynamics simulations. The membrane permeability is currently being assessed. In primary neurons, Aβ42 treatment induces tau hyperphosphorylation, and the reported PROTACs (eg. C004019) can reverse tau hyperphosphorylation to normal levels. The evaluation of our new PROTACs in cell models are being performed according to methods listed above. The development of small-molecule PROTACs may bring breakthrough medicines for AD and other neurodegenerative diseases.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Winblad, B., Wang, L., Sooram, B., Mouskeftara, T., Kumar, R., Weiss, S. S., et al. (2025). Development of small molecules promoting tau degradation in Alzheimer disease. Alzheimer s & Dementia. https://doi.org/10.1002/alz70859_106337
Vancouver
Winblad B, Wang L, Sooram B, Mouskeftara T, Kumar R, Weiss SS, et al. Development of small molecules promoting tau degradation in Alzheimer disease. Alzheimer s & Dementia. 2025. doi:10.1002/alz70859_106337. PMID: 41451568.
BibTeX
@article{winblad2025-41451568,
author = {Winblad, Bengt and Wang, Lisha and Sooram, Banesh and Mouskeftara, Thomai and Kumar, Rajnish and Weiss, Sophia Schedin and Tjernberg, Lars O.},
title = {{Development of small molecules promoting tau degradation in Alzheimer disease}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70859_106337},
pmid = {41451568},
url = {https://doi.org/10.1002/alz70859_106337}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Within around 700 new designed PROTACs, we found by computational modelling more than 25 PROTACs that were predicted to have a better ability to form ternary complexes than the previously reported PROTACs.
- Pharmacokinetic predictions suggested that several PROTACs should have good oral bioavailability, brain permeability and low toxicity.
- Some of the selected PROTACs showed good stability during molecular dynamics simulations.
- The membrane permeability is currently being assessed.
- In primary neurons, Aβ42 treatment induces tau hyperphosphorylation, and the reported PROTACs (eg.
Why it matters
This describes computational design of PROTAC molecules intended to promote tau degradation, with predictions of good oral bioavailability and brain permeability, and notes that membrane permeability and cell model evaluations are still being performed. It is early laboratory work and does not demonstrate any treatment, cure or prevention in people.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Lars O. Tjernberg: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41451568) |
| Free to read | 2 / 2 | Free to read |
| Total | 32 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70859_106337
- PubMed: 41451568
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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