Peripheral oxidative stress related biomarkers in Alzheimer's disease: A systematic review of their implications for diagnosis and disease monitoring

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which oxidative stress drives amyloid beta accumulation and neuronal damage. Fluid-based oxidative stress-related biomarkers offer promising, minimally invasive platforms for early detection, with this review evaluating their diagnostic potential. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of PubMed, Scopus, and Google Scholar identified human studies published between 2000 and 2025 examining fluid-based oxidative stress-related biomarkers in individuals with AD. Elevated lipid peroxidation markers (malondialdehyde, 4-hydroxynonenal, and 1-palmitoyl-2-[5'-oxovaleroyl]-sn-glycero-3-phosphocholine) were consistently linked to AD and cognitive decline. Antioxidant enzymes (superoxide dismutase, glutathione [GSH] peroxidase, and catalase) showed reductions, while GSH and the GSH:oxidized GSH ratio emerged as robust indicators of redox imbalance in AD. Urinary 8-hydroxyguanosine demonstrated compartment-specific sensitivity. Altered trace elements (low selenium, iron, uric acid, and high copper) reflected systemic disruption in AD. Peripheral oxidative stress-related biomarkers offer scalable, minimally invasive avenues for AD diagnosis and monitoring, supporting improved clinical decision making.