Journal article

Culture Variabilities of Human iPSC-Derived Cerebral Organoids Are a Major Issue for the Modelling of Phenotypes Observed in Alzheimer's Disease

Damian Hernandez, Louise A Rooney, Maciej Daniszewski, Lerna Gulluyan, Helena H Liang, Anthony L Cook, Alex W Hewitt, Alice Pebay



Apolipoprotein E (APOE) is the most important susceptibility gene for late onset of Alzheimer's disease (AD), with the presence of APOE-ε4 associated with increased risk of developing AD. Here, we reprogrammed human fibroblasts from individuals with different APOE-ε genotypes into induced pluripotent stem cells (iPSCs), and generated isogenic lines with different APOE profiles. Following characterisation of the newly established iPSC lines, we used an unguided/unpatterning differentiation method to generate six-month-old cerebral organoids from all iPSC lines to assess the suitability of this in vitro system to measure APOE, β amyloid, and Tau phosphorylation levels. We identified variabilit..

View full abstract


Awarded by NHMRC Senior Research Fellowship

Funding Acknowledgements

We thank Sophie Chevalier (CERA), Vikrant Singh (University of Tasmania) and Vanta Jameson (Melbourne Cytometry Platform, Melbourne Brain Centre Node) for technical assistance. This work was supported by grants from the Yulgilbar Alzheimer's Research Program, the DHB Foundation, the Brain Foundation, Dementia Australia, a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (AWH), an NHMRC Senior Research Fellowship (AP, 1154389), the University of Melbourne and Operational Infrastructure Support from the Victorian Government.