Sima does not but ATF4 does induce Ldh. (A) qPCR for Sima in fly heads expressing Aß (Aß+) and un-induced controls (Aß−). Genotype: UAS-Aß; elav GS. (B) qPCR of Ldh in heads from sima mutant flies expressing Aß (Aß sima J11B7+) and their un-induced controls (Aß−, Aß sima J11B7−) Genotypes: UAS-Aß; elav GS/sima J11B7, UAS-Aß; elavGS. **P < 0.01, N = 3–5 per condition. (C) Plot of Performance index for a climbing assay of flies expressing Aß alone (Aß+), together with mutant sima (Aß sima J11B7+) as well as their uninduced controls (Aß−, Aß sima J11B7−). Genotypes as above. UAS-Aß/sima J11B7 genotypes were significantly worse than Aß alone (p = 4.03e-06 respectively by ordinal logistics regression) but there was no interaction with RU, suggesting the sima mutation affects control and Aß expressing flies similarly. Note experiments were run in parallel with Aß+ and Aß− curves in Fig. 3a, but depicted separately for clarity. (D) qPCR for ATF4 in fly heads expressing Aß (Aß+) and un-induced controls (Aß−). Genotype: UAS-Aß; elav GS. (E) qPCR for Ldh in heads from flies expressing Aß together with RNAi for ATF4. Genotypes: UAS-Aß; elavGS/UAS-ATF4 RNAi and UAS-Aß; elav GS. **P < 0.01, N = 3–5 per condition. (F) Plot of Performance index for a climbing assay of flies expressing Aß alone (Aß+), together with RNAi for ATF4 (Aß ATF4RNAi +) and their uninduced controls (Aß− and Aß ATF4RNAi−). Genotypes as above. The Aß ATF4RNAi genotype displayed a significantly worse response to RU over time relative to Aß alone (P = 0.03379 for a three-way interaction of RU, genotype and day by ordinal logistics regression). Note experiments were run in parallel with Aß+ and Aß− curves in Fig. 3a, but depicted separately for clarity.