Loss-of-function TREM2 variants are associated with increased AD risk (van Lengerich et al., 2023) and augment the risk of developing LOAD by 2 to 4 times – similar to the risk associated with APOE ε4 heterozygosity (Corder et al., 1993; Gratuze et al., 2018). This evidence concerns the gene APOE and Alzheimer disease.