Blood biomarkers of amyloid and tau pathologies, brain degeneration, inflammation, and oxidative stress in early- and late-onset Alzheimer's disease

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 ε4 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-α) 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-β (Aβ) 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 Aβ 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 Aβ 42 , p-tau181, NfL, and GFAP showed promise in detecting cognitive decline and AD.