Impaired Oxidative Stress Markers and Activities of Matrix Metalloproteinases in Plasma of Patients with Alzheimer’s Disease, Emphasizing Sex and APOE ε4 Allele Possession

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by Aβ accumulation, tau pathology, and associated oxidative and inflammatory changes, including matrix metalloproteinase (MMP) involvement. This study investigated plasma markers of oxidative damage, carbonyl stress, antioxidant status, and activities of MMP-9 and MMP-2 in AD patients and controls. Spectrophotometric and fluorescent assays were used to assess oxidative and carbonyl stress markers, while MMP activities were measured by gelatin zymography. AD patients exhibited significantly increased protein oxidation, carbonyl stress, and GSH/GSSG ratio, along with reduced total antioxidant capacity and superoxide dismutase activity. Plasma MMP-2 activity was elevated in AD patients, whereas MMP-9 activity showed no significant difference. Notable sex-specific patterns were observed: MMP-2 activity was higher in women with AD than in control women, while MMP-9 activity was increased in men with AD compared with control men. Fructosamine levels were elevated in men regardless of AD status and in AD women versus control women. <i>APOE</i> ε4 status had no significant effect on oxidative stress markers or MMP-9 activity, though higher MMP-2 activity in non-carriers with AD suggests its potential protective role. These findings support the relevance of peripheral biomarkers in AD and indicate sex-dependent pathways that may guide personalized therapeutic strategies.