Down syndrome is a common genetic disorder characterized by a variable clinical presentation, with different phenotypic features. Recently, we showed that olfactory function is already overall impaired in Down syndrome, early in adulthood (Cecchini et al., 2016). The olfactory system is able to distinguish a very large number of odorant molecules and olfactory perception is related to a large range of olfactory receptor genes. In humans, the olfactory receptors genes represent the largest gene family (Buck and Axel, 1991; Glusman et al., 2000; Rouquier et al., 1998) of G protein-coupled receptors. These receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors. They are responsible for the recognition and G protein-mediated transduction of odorant signals (OMIM 164342). Lately, Verbeurgt and co-workers developed a study of olfactory receptors genes expression in the whole human olfactory mucosa obtained post-mortem from 26 subjects (Verbeurgt et al., 2014). The olfactory mucosa contains the first neuronal cells where the olfactory way starts and the olfactory neurons are easily accessible also in living individuals. Recently, our Neurology research group of Verona set up a non-invasive and gentle procedure for olfactory brushing, enabling collecting olfactory neurons. Here we intend to collect olfactory mucosa samples, by means of olfactory brushing technique, in a group of Down syndrome subjects and age matched euploid controls, to investigate the olfactory receptors genes expression. This purpose, to our knowledge for the first time, will contribute to unravel the pattern of expression of olfactory receptors genes in the olfactory mucosa neurons of Down syndrome subjects. This will give new insights for a better comprehension of the olfactory function impairment, yet documented in this pathological condition.