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randomized to receive either Vitamin E 800 IU vitamin C 200 mg alpha lipoic acid 600 mg/day; coenzyme Q 2400 mg per day (800mg 3 times per day), or placebo, for 16 weeks. CSF and plasma were obtained at baseline and after 16 weeks of treatment. Physical examination, blood tests and adverse event reports were used to monitor safety. The MMSE and ADCS-ADL were administered at baseline and week 16. CSF levels of A-beta42, tau and P-tau181 were measured by multiplex assays. F2-isoprostanes are measured by LC-MS methods. Clinical and CSF data were compared between groups using ANCOVA models. Results: 78 subjects with AD (50% women) were randomized. Study medications were well-tolerated, without differences in adverse events between groups. 74 subjects completed treatment and had successful serial lumbar punctures. At baseline, means (SD) were: age 72.8 (9.1), MMSE 22.9 (3.7); these did not differ between treatment arms. CSF levels of A-beta42, tau and P-tau-181 did not differ between treatment arms at baseline. Changes in CSF levels of A-beta42, tau and P-tau181 from baseline to week 16 did not differ between either treatment arm and placebo. Measurements of F2-isoprostanes are in progress. Conclusions: Treatment with a cytosolic antioxidant combination or with CoQ did not alter CSF biomarkers related to A-beta or tau in AD. The supplements, at the doses used, did not appear to influence AD pathologic processes in the brain sufficiently to alter CSF biomarkers. Supported by NIA grant AG10483.