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This study evaluated AD\u2010related blood biomarkers in DS within the AT(N) framework through a systematic review and meta\u2010analysis of studies published between 2017 and October 2024. The meta\u2010analysis focused on plasma amyloid beta (A\u03b2)42, A\u03b240, total tau (t\u2010tau), phosphorylated tau (p\u2010tau)181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels, comparing 2109 DS individuals and 1006 euploid controls. Plasma A\u03b242, A\u03b240, NfL, and GFAP levels were significantly elevated in DS compared to euploid controls, while the A\u03b242\/40 ratio was reduced. In DS\u2010AD individuals, A\u03b242 and t\u2010tau levels were elevated, with p\u2010tau181, NfL, and GFAP consistently high across clinical subgroups. Notably, A\u03b240 and the A\u03b242\/40 ratio changed significantly in preclinical AD, while t\u2010tau increased in clinical AD. Incorporating inflammation (I) markers highlights neuroinflammation's role in DS\u2010AD progression, supporting the blood\u2010based AT(N)I framework for early AD detection and monitoring in DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We reviewed 58 studies on Down syndrome (DS) blood biomarkers and a meta\u2010analysis of 18 using single molecule array.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma amyloid beta (A\u03b2)42, A\u03b240, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels were elevated in DS compared to controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>DS\u2010Alzheimer's disease (AD) individuals showed higher A\u03b242, total tau (t\u2010tau), phosphorylated tau (p\u2010tau)181, NfL, and GFAP levels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma p\u2010tau181, NfL, and GFAP were elevated across all clinical subgroups.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A\u03b240 and A\u03b242\/40 ratio changed in preclinical AD; 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