BACKGROUND: Down syndrome (DS) is associated with a higher risk of diseases linked to advanced glycation end products (AGEs) accumulation. OBJECTIVE: To evaluate serum AGEs and their soluble receptor (sRAGE) levels in children and adolescents with DS and explore associations with anthropometric and biochemical variables. METHODS: A cross-sectional study compared 51 DS participants (ages 3-18) with an age-matched control group (n = 51). Anthropometric measurements, blood chemistry, and lipid profiles were assessed. AGEs and sRAGE concentrations were determined by fluorescence and ELISA, respectively. RESULTS: DS individuals showed an unfavorable lipid profile, with higher triglycerides and lower HDL-C than controls. AGEs concentrations were significantly elevated in DS compared to controls (2.01 ± 0.48 vs. 1.33 ± 0.26 FAU/µg/mL
p <
0.001), while sRAGE levels were reduced (761.3 ± 433.7 vs. 1,196 ± 411.5 pg/mL
p <
0.001). The AGEs/sRAGE ratio was three times higher in the DS group than in controls (3.5 ± 1.9 vs. 1.2 ± 0.4
p <
0.001). Regression analysis identified HbA1c as a strong predictor of increased AGEs in both groups. CONCLUSION: Individuals with DS have an increased risk of dyslipidemia. Additionally, the elevated AGEs/sRAGE ratio associated with this genetic condition may reduce the protective effect of sRAGE against inflammatory processes. IMPACT STATEMENT: This is the first study to evaluate the AGEs/sRAGE ratio alongside biochemical and anthropometric markers in individuals with Down syndrome. DS individuals are at higher risk for dyslipidemia (elevated triglycerides, low HDL-C) and obesity, potentially linked to altered AGEs and sRAGE dynamics. Lower levels of sRAGE in DS may weaken its protective effects against tissue damage and inflammation caused by AGEs accumulation. HbA1c emerged as a strong predictor of AGEs, sRAGE, and the AGEs/sRAGE ratio in the DS cohort, highlighting the importance of monitoring glycemic control.