Our evidence that the TGF-β1/TNF-α ratio, considered a single composite biomarker, is reduced both in young adult individuals with DS and in older adult individuals with DS with or without AD compared to HC and that lower TGF-β1/TNF-α ratio are strongly correlated with the following cognitive decline assessed by the TSI score at T1 should be confirmed in larger observational long-term studies. The gene discussed is TNF; the disease is Alzheimer disease.