Many of the LOAD risk genes, including APOE and TREM2, involve the brain’s immune system and the majority of them are highly enriched in microglia (Gosselin et al., 2017), suggesting glial cells are causally implicated in the pathogenesis of AD, and thus might be important players in the E/I imbalance observed already in the early stages (Henstridge et al., 2019). This evidence concerns the gene APOE and Alzheimer disease.