Downs syndrome (DS) subjects are at high risk of developing Alzheimer's disease (AD). Patients with AD often show altered levels of some immune molecules in their peripheral blood which correlate with cognitive impairment. However, whether the altered peripheral immune phenotype is a late and secondary phenomenon associated with dementia or an early impairment linked to mechanisms controlling neurodegeneration of the central nervous system (CNS) is still an unanswered question. Here we studied immune molecules in the blood of non demented children with DS to investigate whether altered peripheral immune phenotype could be present in these subjects without dementia, many years before the presentation of clinical signs of cognitive deterioration. Plasma levels of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) were significantly higher in DS than in control children. Plasma levels of soluble intercellular adhesion molecule-3 (sICAM-3), soluble vascular cell adhesion molecule-1 (sVCAM-1) and C reactive protein (CRP) were also increased in DS. The increase of IL-6 and CRP from DS children was similar to that found in elderly patients with clinical AD. Peripheral altered immune phenotype in healthy young subjects with DS might be an early sign of CNS alterations leading many years later to cognitive deterioration and dementia.