A 3D human iPSC-derived multi-cell type neurosphere system to model cellular responses to chronic amyloidosis
Our human 3D neurosphere culture system with chronic Aβ exposure reveals how microglia may be essential for the cellular and transcriptional responses in AD pathogenesis. Microglia are not only neuroprotective in neurospheres but also act as key drivers of Aβ-dependent APOE expression suggesting critical roles for microglia in regulating APOE in the AD brain. This novel, well characterized, functional in vitro platform offers unique opportunities to study the roles and responses of microglia to Aβ modelling key aspects of human AD. This tool will help identify new therapeutic targets, accelerating the transition from discovery to clinical applications.
Authors
- Hyun B. Choi (ORCID: https://orcid.org/0000-0003-2405-4428)
- Haakon B. Nygaard (ORCID: https://orcid.org/0000-0001-5085-4723)
- Da Young Kong
- Sarah N. Ebert
- Brian A. MacVicar (ORCID: https://orcid.org/0000-0003-4596-4623)
- Jonathan Frew
- Mathias Delhaye (ORCID: https://orcid.org/0009-0001-3479-5417)
- Konstantina Karamboulas
- Stefano Sorrentino
- Christopher J. Groten (ORCID: https://orcid.org/0000-0002-6063-7295)
- Freda D. Miller (ORCID: https://orcid.org/0000-0001-5104-5557)
- Ian R. Mackenzie (ORCID: https://orcid.org/0000-0003-3875-2972)
- Stefan Wendt (ORCID: https://orcid.org/0000-0002-8754-2464)
- Wenji Cai (ORCID: https://orcid.org/0009-0003-1127-6571)
- Yanyang Bai
- Christopher Lee (ORCID: https://orcid.org/0000-0001-8360-8756)
- Declan J. Brennan
- David R. Kaplan (ORCID: https://orcid.org/0000-0002-4275-8579)
- Ada J. Lin
Institutions
- Vancouver Coastal Health (CA)
- University of British Columbia (CA)
- Université du Québec à Montréal (CA)
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Vancouver General Hospital (CA)
- Canada's Michael Smith Genome Sciences Centre (CA)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1186/s12974-025-03433-3
- Citations
- 1
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.84
Funders
- Krembil Foundation