In AD-DS, tau pathology occurs after the development of extensive Aβ within the brain, and in the general population Aβ accumulation is proposed to trigger tau misfolding, hyper-phosphorylation, mislocalization and accumulation (Braak et al., 2006; Davidson et al., 2018; Wegiel et al., 2022). The gene discussed is MAPT; the disease is Alzheimer disease.