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Study · Animal study (in vivo) · mouse · 2025

5 results

Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.

Zeng PM, Sun XY, Li Y, Wu WD, Huang J, Cao DD, Qian PJ, Ju XC, Luo ZG

Stem cell reports14 Aug 2025Cited by 6 (Europe PMC)

PMID40816274 (opens in a new tab)PMCIDPMC12447315 (opens in a new tab)DOI10.1016/j.stemcr.2025.102601 (opens in a new tab)PepBankPUB-40816274
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Summary

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.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In 5xfAD model mice, beneficial effects of Tβ4 were also revealed; the abstract does not name the outcome.

    In plain wordsIn 5xfAD mice, Tβ4 also had beneficial effects. The abstract does not say which ones.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    Direction not reportedBeneficial effects of Tβ4 (outcome not specified)
    Study

    mousen: not reported in source

    5xfAD model mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The beneficial effects of Tβ4 were also revealed in 5xfAD model mice.
  2. 02LabIn vitro (cells)Efficacy outcome

    In cerebral organoids with familial Alzheimer disease APP mutations, treatment with Tβ4 rescued the neurodevelopmental deficits.

    In plain wordsIn lab-grown brain organoids with Alzheimer-linked mutations, Tβ4 reversed problems in nerve cell development.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseNeurodevelopmental deficits in fAD organoids
    Study

    humann: not reported in source

    iPSC-derived cerebral organoids with familial AD APP mutations
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Remarkably, the neurodevelopmental deficits and Aβ formation in fAD organoids were rescued by treatment with Tβ4.
    1 context sentence
    Summary · context
    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.
  3. 03LabIn vitro (cells)Efficacy outcome

    In cerebral organoids with familial Alzheimer disease APP mutations, treatment with Tβ4 rescued β-amyloid (Aβ) formation.

    In plain wordsIn lab-grown brain organoids with Alzheimer-linked mutations, Tβ4 reduced the build-up of amyloid protein.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseAβ formation in fAD organoids
    Study

    humann: not reported in source

    iPSC-derived cerebral organoids with familial AD APP mutations
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Remarkably, the neurodevelopmental deficits and Aβ formation in fAD organoids were rescued by treatment with Tβ4.
    1 context sentence
    Summary · context
    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.

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 04HumanEndogenous levelObservational studyMechanism

    In patients with Alzheimer disease, expression of TMSB4X (the gene for Tβ4) was significantly decreased in excitatory neurons.

    In plain wordsIn people with Alzheimer disease, the gene for the body's own Tβ4 was less active in excitatory neurons.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseTMSB4X expression in excitatory neurons of AD patients
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    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.

    This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.

  2. 05LabEndogenous levelIn vitro (cells)Mechanism

    In cerebral organoids with familial Alzheimer disease APP mutations, expression of TMSB4X (the gene for Tβ4) was significantly decreased in neurons.

    In plain wordsIn lab-grown brain organoids with Alzheimer-linked mutations, the gene for the body's own Tβ4 was less active in neurons.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseTMSB4X expression in fAD organoid neurons
    Study

    humann: not reported in source

    iPSC-derived cerebral organoids with familial AD APP mutations
    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    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.
    1 context sentence
    Summary · context
    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.

    This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 01:52 UTC

    Study results updated

  2. Version 1

    12 Oct 2026, 18:17 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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