@article{bibcite_8851,
  keywords = {Alzheimer{\textquoteright}s disease, Experimental models of disease, induced pluripotent stem cells, Neurodegeneration, Neuroimmunology},
  author = {Julien Klimmt and Carolina Cardoso Gon{\c c}alves and Jessica Valentina Montgomery and Stephan A. M{\"u}ller and Merle Bublitz and Severin Filser and Lars Paeger and Brigitte Nuscher and Angelika Dannert and Sigrun Roeber and Veronica Pravata and Martina Schifferer and Joshua J. Shrouder and Nathalie Schulz and Judit Gonz{\'a}lez-Gallego and Silvia Cappello and Thomas Misgeld and Nikolaus Plesnila and Eduardo Beltr{\'a}n and Jochen Herms and Elena De Domenico and Marc D. Beyer and Joachim L. Schultze and Christian Haass and Stefan F. Lichtenthaler and Caterina Carraro and Dominik Paquet},
  title = {A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes},
  abstract = {Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions, but limitations in reproducibility, maturation and cell-type diversity persist. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a human induced pluripotent stem cell-based three-dimensional cortical brain tissue model (3BTM) containing neurons, astrocytes and microglia with high reproducibility, maturity and viability. 3BTMs show morphological, functional and proteomic maturation of all cell types, leading to high similarity to their in vivo counterparts. Incorporated microglia survive for over 6 months and display mature morphology, functions and gene expression. Importantly, when engineered to model Alzheimer{\textquoteright}s disease pathology, 3BTMs recapitulate key disease hallmarks, including amyloid deposition, increased phospho-tau levels and neuroinflammation, with microglia shifting their transcriptional landscape to disease-relevant signatures. Treatment of Alzheimer{\textquoteright}s disease 3BTMs with anti-Aβ immunotherapy cleared deposits and largely reversed disease signatures in glia. Together, our microglia-containing model provides a platform for studying physiological and pathological states of human brain tissue.},
  year = {2026},
  journal = {Nature Neuroscience},
  pages = {1-17},
  month = {2026-08-04},
  issn = {1546-1726},
  url = {https://www.nature.com/articles/s41593-026-02367-0},
  doi = {10.1038/s41593-026-02367-0},
  language = {en},
}