Rab5 and Endo A ameliorates Aβ42 toxicity. (A) Survival curves of flies expressing Aβ, with (red lines, UAS-Aβ/+; elavGS/UAS-Rab5) and without (black lines, UAS-Aβ/+; elavGS/+) Rab5 co-overexpression, in adult neurons (RU200, solid lines) and uninduced controls (RU0, dashed lines). Co-overexpression of Rab5 extended lifespan of Aβ-expressing flies. n > 120 per condition. Aβ RU0 versus Aβ RU200, P = 7.46192E−76; Aβ RU0 versus Aβ Rab5 RU0, P = 6.07338E−05; Aβ Rab5 RU0 versus Aβ Rab5 RU200, P = 1.54498E−70; Aβ RU200 versus Aβ Rab5 RU200 P = 6.06826E−22, determined by log–rank test. There was a significant interaction of genotype and RU by Cox proportional hazard analysis, P = 0.000338, indicating that expression of Rab5 significantly extended the lifespan of Aß-expressing flies. (B) Survival curves of flies expressing Aβ, with (red lines, UAS-Aβ/UAS-EndoA; elavGS/+) and without (black lines, UAS-Aβ/+; elavGS/+) EndoA co-overexpression, in adult neurons (RU200, solid lines) and uninduced controls (RU0, dashed lines). Co-overexpression of EndoA extended lifespan of Aβ-expressing flies. n > 120 per condition. Aβ RU0 versus Aβ RU200, P = 7.46192E−76; Aβ RU0 versus Aβ EndoA RU0, P = 0.007893292; Aβ EndoA RU0 versus Aβ EndoA RU200, P = 5.2333E−70; Aβ RU200 versus Aβ EndoA RU200 P = 1.42894E−26, determined by log–rank test. There was a significant interaction of genotype and RU by Cox proportional hazard analysis, P < 2E−16, indicating that expression of EndoA significantly extended the lifespan of Aß-expressing flies. (C) Locomotor performance index of induced flies of the same genotypes as in (A). Co-overexpression of Rab5 did not effect climbing ability by ordinal logistics regression (P = 0.62), n = ~50 flies per condition. (D) Locomotor performance index of induced flies of the same genotypes as in (B). Co-overexpression of EndoA worsened the climbing ability of Aß flies but slowed down the decline relative to Aß-expressing flies alone, P = 3.3867E−06 for effect of genotype (z value = −4.6), P = 0.00011043 for interaction between genotype and time (z value = 3.9), n = ~50 flies per condition.