Down syndrome is the most common chromosomal disorder, caused by a third copy of all or part of chromosome 21 (HSA21), and the most complex and prevalent genetic cause of intellectual disability. 1 It is a chronic, multifactorial disorder that affects brain development and function, impairing cognition and adaptive behaviour. 2 Moreover, Down syndrome co-occurs with autism and epilepsy and is considered a genetic form of Alzheimer disease. 3 In addition, individuals with Down syndrome have a high prevalence of endocrine disorders and obesity, leading to type 2 diabetes, insulin resistance, and neuroinflammation, 4 which, in turn, contribute to cognitive deficits.In the last decade, an important effort was made to better understand the pathogenetic mechanisms involved in Down