In mixed AD and diabetic mice using APPswe/PS1dE9 (APP/PS1) transgenic AD model or triple-transgenic model of AD (3xTg-AD) with either STZ treatment or InsR deficiency (db/db), genetic background and dysfunctional insulin signaling cooperatively exacerbated CNS inflammation and AD pathology (Hierro-Bujalance et al., 2020; Imamura et al., 2020; Sankar et al., 2020). Here, INSR is linked to Alzheimer disease.