MAPT and Alzheimer disease: By the age of 40, people with DS develop a pathological profile consisting of amyloid plaques and tau containing neurofibrillary tangles (NFTs) within the neo and limbic cortex similar to Alzheimer's disease (AD) (Wisniewski et al., 1985; Davidson et al., 2018) as well as reduction in brain volume (de la Monte and Hedley-Whyte, 1990; Weis et al., 1991; Kesslak et al., 1994; Aylward et al., 1999; Teipel et al., 2003; Edgin et al., 2015; Cipriani et al., 2018), including the cerebellum (Weis et al., 1991; Jernigan et al., 1993).