Significant modifications of the salivary proteome potentially associated with complications of Down syndrome revealed by top-down proteomics

People with Down syndrome, a frequent genetic disorder in humans, have increased risk of health problems associated with this condition. One clinical feature of Down syndrome is the increased prevalence and severity of periodontal disease in comparison with the general population. Since saliva plays an important role in maintaining oral health, in the present study the salivary proteome of Down syndrome subjects was investigated to explore modifications with respect to healthy subjects. Whole saliva of 36 Down syndrome subjects, divided in the age groups 10-17 yrs and 18-50 yrs, was analyzed by a top-down proteomic approach, based on the HPLC-ESI-MS analysis of the intact proteins/peptides, and the qualitative and quantitative profiles were compared with sex and age-matched control groups. The results showed the following interesting features: i) differently from controls, in Down syndrome subjects the concentration of the major salivary proteins of gland origin did not increase with age; as a consequence concentration of acidic proline rich proteins and S cystatins was found significantly reduced in older Down syndrome subjects with respect to matched controls; ii) levels of the antimicrobial α-defensins 1 and 2 and histatins 3 and 5 were significantly increased in whole saliva of older Down syndrome subjects with respect to controls; iii) S100A7, S100A8 and S100A12 levels were significantly increased in whole saliva of Down syndrome subjects in comparison with controls. The increased level of S100A7 and S100A12 may be of particular interest, as biomarker of the early onset Alzheimer's disease, which is frequently associated with Down syndrome.