To obtain further understanding in whether global genetic risk for Alzheimer’s Disease, as measured by a polygenic risk score, can affect the function of microglia, the brain’s immue cells, and their response to amyloid-beta pathology, one of the major hallmarks of the disease. From the Flemish in-house cohorts from the UZ Leuven all individuals were scored on a range from increased to decreased risk for the development of Alzheimer’s Disease. This selection was based on the APOE genotype (Ɛ3/Ɛ3, Ɛ4/Ɛ4 and Ɛ3/Ɛ4) and PRS-AD such that patients are selected from the low and high PRS end. In total 15 individuals have been identified with high and low genetic risk for Alzheimer’s Disease that could be used for iPSC generation.

From the blood cells from these selected donors, induced pluripotent stem cells (iPCSs) were created. These iPSCs were created in collaboration with the KU Leuven Stem Cell Institute and the iPSC Hotel at Leiden University. In total 13 independent iPSC lines with 3 clones each were successfully generated. Due to the low quality, the blood cells from 2 individuals failed to be reprogrammed. All lines have been successfully characterized and passed all quality control checks for pluripotency, stemness and lacked major genetic aberrations introduced during the reprogramming process. Two scientific publications related to these activities are in development and are slated for submission by the end of 2024.

The iPSC lines created, have been shared with other consortium partners for further in vitro and in vivo characterization. A standard protocol has been developed by VIB and shared with the other consortium partners to differentiate iPSCs into microglia.