Faculty, Staff and Student Publications
A Neuroimmune Cerebral Assembloid Model to Study the Pathophysiology of Familial Alzheimer's Disease
Language
English
Publication Date
10-8-2025
Journal
Journal of Neuroinflammation
DOI
10.1186/s12974-025-03544-x
PMID
41063316
PMCID
PMC12509420
PubMedCentral® Posted Date
10-8-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Alzheimer's disease (AD) is the leading cause of dementia globally. The accumulation of amyloid and tau proteins, neuronal cell death and neuroinflammation are seen with AD progression, resulting in memory and cognitive impairment. Microglia are crucial for AD progression as they engage with neural cells and protein aggregates to regulate amyloid pathology and neuroinflammation. Recent studies indicate that microglia contribute to the propagation of amyloid beta (Aβ) via their immunomodulatory functions including Aβ phagocytosis and inflammatory cytokine production. Three-dimensional cell culture techniques provide the opportunity to study pathophysiological changes in AD in human-derived samples that are difficult to recapitulate in animal models (e.g., transgenic mice). However, these models often lack immune cells such as microglia, which play a critical role in AD pathophysiology. In this study, we developed a neuroimmune assembloid model by integrating cerebral organoids (COs) with induced microglia-like cells (iMGs) derived from human induced pluripotent stem cells from familial AD patient with PSEN2 mutation. After 120 days in culture, we found that iMGs were successfully integrated within the COs. Interestingly, our assembloids displayed histological, functional and transcriptional features of the pro-inflammatory environment seen in AD, including amyloid plaque-like and neurofibrillary tangle-like structures, reduced microglial phagocytic capability, and enhanced neuroinflammatory and apoptotic gene expression. In conclusion, our neuroimmune assembloid model effectively replicates the inflammatory phenotype and amyloid pathology seen in AD.
Keywords
Alzheimer Disease, Humans, Microglia, Organoids, Induced Pluripotent Stem Cells, Animals, Amyloid beta-Peptides, Cells, Cultured, Alzheimer’s disease, Stem cells, Cerebral organoids, Microglia, Assembloids, Neuroinflammation, Amyloid beta
Published Open-Access
yes
Recommended Citation
Becerra-Calixto, Andrea; Banerjee, Anik; Fan, Huihui; et al., "A Neuroimmune Cerebral Assembloid Model to Study the Pathophysiology of Familial Alzheimer's Disease" (2025). Faculty, Staff and Student Publications. 5630.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5630
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