Abstract: The triplication of chromosome 21 causes Down syndrome (DS), a genetic disorder that is characterized by intellectual disability (ID). The causes of ID start in utero, leading to impairments in neurogenesis, and continue into infancy, leading to impairments in dendritogenesis, spinogenesis, and connectivity. These defects are associated with alterations in mitochondrial and metabolic functions and precocious aging, leading to the early development of Alzheimer's disease. Intense efforts are currently underway, taking advantage of DS mouse models to discover pharmacotherapies for the neurodevelopmental and cognitive deficits of DS. Many treatments that proved effective in mouse models may raise safety concerns over human use, especially at early life stages. Accumulating evidence shows that fatty acids, which are nutrients present in normal diets, exert numerous positive effects on the brain. Here, we review (i) the knowledge obtained from animal models regarding the effects of fatty acids on the brain, by focusing on alterations that are particularly prominent in DS, and (ii) the progress recently made in a DS mouse model, suggesting that fatty acids may indeed represent a useful treatment for DS. This scenario should prompt the scientific community to further explore the potential benefit of fatty acids for people with DS.
