Home › Research › Disease mechanisms
Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities
Lisha Wang, Banesh Sooram, Rajnish Kumar, Sophia Schedin-Weiss, Lars O Tjernberg, Bengt Winblad. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-03
Topic: Disease mechanisms in lab and animal studies
In Alzheimer's disease (AD), tau undergoes abnormal post-translational modifications and aggregations. Impaired intracellular degradation pathways further exacerbate the accumulation of pathological tau. A new strategy - targeted protein degradation - recently emerged as a modality in drug discovery where bifunctional molecules bring the target protein close to the degradation machinery to promote clearance. Since 2016, this strategy has been applied to tau pathologies and attracted broad interest in academia and the pharmaceutical industry. However, a systematic review of recent studies on tau degradation mechanisms is lacking. Here we review tau degradation mechanisms (the ubiquitin-proteasome system and the autophagy-lysosome pathway), their dysfunction in AD, and tau-targeted degraders, such as proteolysis-targeting chimeras and autophagy-targeting chimeras. We emphasize the need for a continuous exploration of tau degradation mechanisms and provide a future perspective for developing tau-targeted degraders, encouraging researchers to work on new treatment options for AD patients. HIGHLIGHTS: Post-translational modifications, aggregation, and mutations affect tau degradation. A vicious circle exists between impaired degradation pathways and tau pathologies. Ubiquitin plays an important role in complex degradation pathways. Tau-targeted degraders provide promising strategies for novel AD treatment.
Key findings
- We emphasize the need for a continuous exploration of tau degradation mechanisms and provide a future perspective for developing tau-targeted degraders, encouraging researchers to work on new treatment options for AD patients.
- HIGHLIGHTS: Post-translational modifications, aggregation, and mutations affect tau degradation.
- A vicious circle exists between impaired degradation pathways and tau pathologies.
- Ubiquitin plays an important role in complex degradation pathways.
- Tau-targeted degraders provide promising strategies for novel AD treatment.
Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 75/100
Published in a leading specialty journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 42 of the 56 points we could judge it on, which is 75 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomisation is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40109019) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 42 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 42 of the 56 points we could judge it on is 75 out of 100. |
| Total | 75 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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. Check the citation against the original before you use it.
APA 7th
Wang, L., Sooram, B., Kumar, R., Schedin-Weiss, S., Tjernberg, L. O., & Winblad, B. (2025). Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70048
Vancouver
Wang L, Sooram B, Kumar R, Schedin-Weiss S, Tjernberg LO, Winblad B. Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70048. PMID: 40109019.
BibTeX
@article{wang2025-40109019,
author = {Wang, Lisha and Sooram, Banesh and Kumar, Rajnish and Schedin-Weiss, Sophia and Tjernberg, Lars O and Winblad, Bengt},
title = {{Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70048},
pmid = {40109019},
url = {https://doi.org/10.1002/alz.70048}
}
Related studies in Disease mechanisms
Also tagged “phosphorylation”
387 studies in the library carry the topic tag “phosphorylation”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 387 tagged studies.