(A) Neurodegeneration was significantly reduced by coexpressing tau^R406W with Tpx1 (***P < 0.001) or with Sod2 (***P < 0.001). Neuronal cell death in tau^R406W transgenic flies that have increased expression of Tpx1 (P < 0.05) or of Sod2 (P < 0.01) was still significantly higher than in controls, indicating that tau-induced neurotoxicity was not completely rescued by these increased antioxidant activities. Quantification of TUNEL-positive cells in the brains of 10-day-old flies was used to evaluate neurotoxicity in controls and in tau^R406W transgenics coexpressing either β-gal (control transgene), Tpx1, or Sod2. Genotypes are as follows: control, elav-GAL4/+; tau^R406W + β-gal, elav-GAL4/+, UAS-lacZ/+, UAS-tau^R406W/+; tau^R406W + Tpx1, elav-GAL4/+, UAS-Tpx1/+, UAS-tau^R406W/+; and tau^R406W + Sod2, elav-GAL4/+, UAS-Sod2⁴¹/+, UAS-tau^R406W/+. (B) Administration of vitamin E for 10 days after eclosion suppressed tau-induced neurodegeneration. TUNEL assay quantification measured apoptosis in the brains of tau^R406W-expressing flies and control flies fed with soybean oil solvent (control) or with the indicated doses of vitamin E. Tau-induced neurodegeneration was significantly suppressed in tau^R406W transgenic flies by feeding with 0.5 mM (***P < 0.001) or 1.5 mM (***P < 0.001) of vitamin E compared with feeding with solvent only. Treatment of tau^R406W transgenic flies with vitamin E did not completely abolish neuronal cell death, since toxicity was still significantly higher (P < 0.001) than in control flies. Error bars indicate ± SEM. Genotypes are as follows: control, elav-GAL4/+; and tau^R406W, elav-GAL4/+, UAS-tau^R406W/+.