By the fourth decade of their lives, all individuals with DS develop Alzheimer’s disease (AD) neuropathology, including the accumulation of amyloid plaques comprising β-amyloid (Aβ) peptides, neurofibrillary tangles (NFTs) formed by insoluble deposits of abnormally hyperphosphorylated tau, synaptic and neuronal loss, reduced neurogenesis, regional atrophy, and chronic microglial-driven inflammatory response, which leads to dementia (Teipel and Hampel, 2006; Sabbagh et al., 2011; Cenini et al., 2012; Lott, 2012; Wilcock and Griffin, 2013; Moreno-Jiménez et al., 2019). Here, MAPT is linked to Alzheimer disease.