Munich, August 4, 2026 – After decades of intensive global research, a significant hurdle in Alzheimer’s disease research has been the lack of three-dimensional models that accurately represent the complex interactions within human brain tissue. Now, a team led by neuroscientist Professor Dominik Paquet from LMU Klinikum has made substantial progress in this area, developing a novel 3D brain tissue model. Their findings have been published in the prestigious journal ‘Nature Neuroscience’.
Overcoming the Limitations of Traditional Models
Professor Dr. Dominik Paquet from the Institute for Stroke and Dementia Research at LMU Klinikum emphasized the previous limitations: “Until now, there was a lack of three-dimensional models that realistically depict the complex interrelationships in human brain tissue in Alzheimer’s dementia.” This new development holds potentially far-reaching implications for the creation of new Alzheimer’s medications.
The process, which may sound like magic to the uninitiated, involves cultivating tissue from stem cells that closely resemble human originals. Paquet describes it as “pure scientific creativity and craftsmanship,” coupled with immense patience. “It took us nine years,” he stated, “to develop our new, three-dimensional model of human brain tissue until it functioned on all necessary levels.” For Alzheimer’s research, functioning on all necessary levels means focusing on the interaction of various cell types and their biochemical functions, rather than merely replicating the brain’s exact structure.
The Right Recipe for Authentic Interplay
The new 3D tissue model originates from human stem cells, which can be transformed into different types of brain cells, specifically nerve cells, astrocytes, and microglial cells. To achieve this, the stem cells must be treated with a precise “cocktail of various substances, according to a very specific recipe that we developed ourselves,” Paquet explained.
In a specialized nutrient solution, these differentiated cells connect and adhere to each other. Paquet further elaborated, “Within a week, tissue spheres the size of half a pinhead form, which organize themselves and take on central functions of the brain.”
(Almost) Everything as in a Real Human Brain
The nerve cells in these models form extensions and connect with functional synapses. Astrocytes provide nutrients to their neighbors, while microglial cells – the brain’s immune cells – monitor their environment, ensuring that no dead cells or foreign substances accumulate where they shouldn’t. “We also checked whether all important genes and proteins relevant for the study of Alzheimer’s dementia are active in our tissue model,” the neuroscientist confirmed, “and that is definitely the case.”
Reproducible, Modifiable, and Disease-Relevant
Another significant advantage of this system is its reproducibility. Following the Munich researchers’ instructions, tissue structures with the same composition and functions can be reliably generated. “From the outside, however, we can change the generated brain tissue,” Dominik Paquet noted, “for example, induce symptoms of a disease like Alzheimer’s, test potential drugs, and so on.” Indeed, the researchers successfully induced the formation of Alzheimer-typical amyloid aggregates and then dissolved them using new, already available drugs. Crucially, microglia, which play a central role in the disease, were demonstrably active during this process.
Next Step: Automation for Efficient Drug Development
“Our system,” Dominik Paquet believes, “could help accelerate the development of new drugs.” With this in mind, his team is currently working on automating and scaling the production of these tissue models using robots. The goal is to produce hundreds to thousands of tissues exhibiting the same disease symptoms. This is particularly vital for industrial applications, allowing for the efficient testing of numerous new substances for their effectiveness against Alzheimer’s within a human system.
Scientific Contact:
Prof. Dr. rer. nat. Dominik Paquet
Professor of Neurobiology
Institute for Stroke and Dementia Research (ISD)
LMU Klinikum München, Campus Großhadern
Tel: +49 89 4400-46123
E-Mail: [email protected]
Original Publication:
Klimmt, J., Cardoso Gonçalves, C., Montgomery, J.V. et al. A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes. Nature Neuroscience (2026). DOI: https://doi.org/10.1038/s41593-026-02367-0
