APOE and Alzheimer disease: Our systematic literature search showed that the process of cytokine release by glia to maintain homoeostasis and respond to damage is dysfunctional in the ageing and AD brain 96, with substantial evidence pointing towards the APOE4 allele playing a crucial role in this 97, 98, 99, supporting the transcriptional profile changes seen in ε4 microglia and astrocytes.