Abstract: Down syndrome (DS) is the most frequent chromosomal abnormality that causes intellectual disability, resulting from the presence of an extra complete or segment of chromosome 21 (HSA21) (Tramutola et al., 2020; Lanzillotta et al., 2021). Every year, approximately 6000 children are born with DS and most of them do not have an autonomous life. Thanks to the advancement in medical care, DS individuals live long and often outlive their parents (Lott and Head, 2019). As a consequence, individuals with DS are now experiencing a high incidence of age-associated health problems, especially Alzheimer’s disease (AD) dementia (Lott and Head, 2019). In particular, by the age of 40 years, virtually all individuals with DS show AD neuropathology (Lott and Head, 2019). The link between AD and DS is thought to be mainly related to the triplication of the amyloid precursor gene (APP), which is encoded on HSA21. However, trisomy of HSA21 results in increased gene dosage for other genes in addition to APP, which may also be involved in AD development. These include superoxide dismutase 1, which is involved in redox metabolism; adenosine triphosphate (ATP)-binding cassette sub-family G member 1, which is involved in cholesterol metabolism; cystatin B, beta-secretase 2, and synaptojanin 1 involved in beta-amyloid (Aβ) processing and clearance; the dual-specificity tyrosine phosphorylation-regulated kinase-1A, which is involved in Tau phosphorylation; regulator of calcineurin, which is involved in mitochondrial dysfunction; S100B involved in inflammatory responses (Lott and Head, 2019).