Studies in human post-mortem brain tissue have demonstrated that synaptic oligomeric Aβ and synapse loss are most prominent in the vicinity of Aβ plaques and accumulate to a greater degree in APOE ε4 carriers55–57, so future work exploring the impact of patient characteristics in response to Aβ challenge in HBSCs may help provide mechanistic insight into the relationship between APOE genotype and AD risk. This evidence concerns the gene APOE and Alzheimer disease.