Several studies show that DS adults carrying the APOE ε4 allele face a higher risk (Prasher et al., 2008) of developing AD dementia and tend to have an earlier age of onset (Bejanin et al., 2021; Silverman et al., 2013) and a higher degree of cognitive decline (Gorijala et al., 2024) and earlier changes in amyloid (cerebrospinal fluid Aβ1-42/1-40 and amyloid positron emission tomography), tau (plasma phosphorylated tau 181), and neurodegeneration (cerebral glucose hypometabolism and hippocampal atrophy) biomarkers (Bejanin et al., 2021). The gene discussed is MAPT; the disease is hippocampal atrophy.