While current literature in the field is largely focused on investigating microglial pathways that confer increased risk for developing AD (e.g. TREM2, APOE, PLCγ2), disease-modifying SNPs around microglial genes, particularly the loss-of-function CX3CR1-V249I variant, have been associated with increased neuronal loss and disease severity in macular degeneration, ALS and AD [7, 8, 38]. This evidence concerns the gene APOE and amyotrophic lateral sclerosis.