Background Numerous blood biomarkers have emerged as promising biomarkers for Alzheimer's disease (AD) and cognitive decline, but limited knowledge exists concerning the difference of blood biomarkers between early-onset and late-onset cases. Objective Investigate blood biomarkers associated with amyloid and tau pathologies, brain degeneration, inflammation, and oxidative stress in individuals afflicted with both early-onset and late-onset AD, as well as in age-matched healthy controls. Methods A total of 125 participants were enrolled. We assessed levels of 18 distinct blood biomarkers and their associations with cerebrospinal fluid biomarkers, neuropsychological test scores, APOE epsilon 4 carrier status, and neuroimaging markers. The diagnostic potential of blood biomarkers was investigated. Results In early-onset AD patients, levels of blood Interleukin (IL)-4, IL-6, and Tumor necrosis factor-alpha (TNF-alpha) were notably lower comparing to late-onset patients. AD patients exhibited higher blood levels of phosphorylated-tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), as well as lower levels of amyloid-beta (A beta)(42) and IL-12p70. Oxidative stress markers, including malondialdehyde, total antioxidant capacity, and superoxide dismutase, exhibited a progressive trend across the continuum of AD. Inflammatory markers demonstrating correlations with neuroimaging markers. Blood levels of A beta(42), p-tau181, NfL, and GFAP associated with neuropsychological scores and effectively discriminated AD, with GFAP exhibiting particular relevance in early-onset cases. Conclusions Inflammatory markers exhibited differences between patients with early- and late-onset AD, associated with alterations in brain structure and function. With the progression of disease continuum, a decrement in antioxidant capacity was observed. Blood A beta(42), p-tau181, NfL, and GFAP showed promise in detecting cognitive decline and AD.