Breakthrough in Alzheimer's Research: Brain Organoids Reveal New Treatment Targets

Alzheimer's disease (AD), the leading cause of neurodegeneration among older adults, affects approximately 1 in 20 individuals aged 65 and above. While environmental and lifestyle factors contribute to disease risk, genetic mutations play a significant role, especially in familial Alzheimer's disease (fAD), which tends to develop earlier. Traditionally diagnosed at advanced stages, early pathological changes in brain cells can occur long before symptoms become evident, particularly in genetic forms of AD.

Recent advancements utilize stem cell-derived brain organoids to model early brain development and uncover initial disease mechanisms. Researchers from ShanghaiTech University led by Zhen-Ge Luo have used these organoids to study early-stage AD features. Their work, published in Stem Cell Reports, demonstrated that organoids derived from fAD patients recapitulate hallmark pathologies such as increased amyloid protein accumulation, reduced mature neurons, and higher cell death rates compared to healthy controls. Additionally, gene expression analyses revealed distinct alterations, notably in the TMSB4X gene, which encodes the anti-inflammatory protein Thymosin β4 (Τβ4). Interestingly, decreased TMSB4X levels were observed not only in organoid models but also in brain tissue samples from deceased AD patients.

Building on this discovery, the team experimented with administering Τβ4 to fAD organoids. Results showed a reduction in amyloid protein levels, an increase in healthy neurons, and gene expression normalization, suggesting potential therapeutic effects. Extending this approach to animal models, mice harboring fAD mutations received Τβ4 treatment, which successfully elevated Τβ4 levels in the brain, lowered amyloid accumulation, and corrected gene expression abnormalities. Furthermore, Τβ4 appeared to mitigate brain inflammation and neuronal overactivation, common features of AD.

This pioneering research highlights how brain organoids can be instrumental in identifying novel intervention targets for Alzheimer's disease. While promising, further studies are essential to evaluate the safety and efficacy of Τβ4 in human patients, its potential to delay disease onset in mutation carriers, and its therapeutic role in existing AD cases.

Source: https://medicalxpress.com/news/2025-08-alzheimer-disease-pathology-potential-treatment.html