In response to this need, more than 180 transgenic/knock-out/knock-in AD models have been developed that are mostly centered alone or in combination with human gene mutations in APP, presenilin 1 (PSEN1), apolipoprotein E (APOE), microtubule-associated protein tau (MAPT), and triggering receptor expressed on myeloid cells2 (Trem2) or Beta-Secretase 1 (BACE1). This evidence concerns the gene APOE and Alzheimer disease.