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Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids
Peng-Ming Zeng, Xin-Yao Sun, Yang Li, Wen-di Wu, Jing Huang, Dongdong Cao, Pin-jue Qian, Xiang-Chun Ju et al.. Stem Cell Reports, 2025-08-15
Topic: Brain proteins, microglia and lab models
The developmental origin of Alzheimer disease (AD) has been proposed but is arguably debated. Here, we developed cerebral organoids from induced pluripotent stem cells (iPSCs) with mutations in amyloid precursor protein (APP) associated with familial AD (fAD) and analyzed the dynamic changes of cellular states. We found that mature neurons induced in fAD organoids markedly decreased compared to that of health control, accompanied with increased cell senescence and β-amyloid (Aβ) production. Interestingly, the expression level of the gene TMSB4X that encodes thymosin beta 4 (Tβ4) significantly decreased both in fAD organoids' neurons and AD patients' excitatory neurons. Remarkably, the neurodevelopmental deficits and Aβ formation in fAD organoids were rescued by treatment with Tβ4. The beneficial effects of Tβ4 were also revealed in 5xfAD model mice. Thus, this study has identified Tβ4 as a neuroprotective factor that may mitigate altered neurogenesis and AD pathology, highlighting a potential for disease intervention.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zeng, P.-M., Sun, X.-Y., Li, Y., Wu, W.-d., Huang, J., Cao, D., et al. (2025). Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2025.102601
Vancouver
Zeng P.-M, Sun X.-Y, Li Y, Wu W.-d, Huang J, Cao D, et al. Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids. Stem Cell Reports. 2025. doi:10.1016/j.stemcr.2025.102601. PMID: 40816274.
BibTeX
@article{zeng2025-40816274,
author = {Zeng, Peng-Ming and Sun, Xin-Yao and Li, Yang and Wu, Wen-di and Huang, Jing and Cao, Dongdong and Qian, Pin-jue and Ju, Xiang-Chun and others},
title = {{Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids}},
journal = {Stem Cell Reports},
year = {2025},
doi = {10.1016/j.stemcr.2025.102601},
pmid = {40816274},
url = {https://doi.org/10.1016/j.stemcr.2025.102601}
}
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Key findings
- Here, we developed cerebral organoids from induced pluripotent stem cells (iPSCs) with mutations in amyloid precursor protein (APP) associated with familial AD (fAD) and analyzed the dynamic changes of cellular states.
- We found that mature neurons induced in fAD organoids markedly decreased compared to that of health control, accompanied with increased cell senescence and β-amyloid (Aβ) production.
- Interestingly, the expression level of the gene TMSB4X that encodes thymosin beta 4 (Tβ4) significantly decreased both in fAD organoids' neurons and AD patients' excitatory neurons.
- The beneficial effects of Tβ4 were also revealed in 5xfAD model mice.
Why it matters
Using human brain organoids carrying familial Alzheimer's APP mutations, this study found fewer mature neurons, more cell senescence and more Aβ production, and treatment with thymosin beta 4 rescued these deficits; beneficial effects were also seen in 5xfAD model mice. This identifies Tβ4 as a potential neuroprotective factor for disease intervention, but the work is at the organoid and animal stage and has not been tested in patients.
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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 (Stem Cell Reports) |
| Journal's citation record | 1 / 4 | Stem Cell Reports: journal h-index 146 (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 “organoids”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 10 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.5× 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 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Zhen‐Ge Luo: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Chinese Academy of Sciences: institution h-index 1,801 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40816274) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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Read the original
- DOI: 10.1016/j.stemcr.2025.102601
- PubMed: 40816274
- Original source →
- Free full text: Stem Cell Reports →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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