Figure 1
Aβ42 expression level dictates the onset of memory impairments in a Drosophila model of Alzheimer’s disease. (a) Protein extracts from heads of flies raised at 25 °C or 27 °C were immunodetected for Aβ42 and β-Tubulin. (b) Aβ42 levels were quantified and normalized to the amount of β-Tubulin for control flies (UAS-LacZ/+; ok107-Gal4/+ and UAS-Aβ42/+) and flies expressing Aβ42 in the MBs (UAS-Aβ42/+; ok107-Gal4/+) at both temperatures. (c,d) Flies were raised at either 25 °C (c) or 27 °C (d) throughout development and up to day 1, 5, 15 or 30 post-eclosion and then trained using olfactory classical conditioning. Flies were tested immediately after conditioning. Memory performance index (P.I.) is shown for control flies (UAS-LacZ/+; ok107-Gal4/+) and flies expressing Aβ42 in the MB neurons (UAS-Aβ42/+; UAS-LacZ/+; ok107-Gal4/+). (c) At 25 °C, control flies show normal memory decay through aging (day 1 vs day 5, p = 0.5202; day 5 vs day 15, p = 0.0005; day 15 vs day 30, p = 0.9215). Expression of the Aβ42 peptide in the MB neurons (UAS-Aβ42/+; UAS-LacZ/+; ok107-Gal4/+) enhances this memory decline (day 1 vs day 5, p = 0.1031; day 5 vs day 15, p = < 0.0001; day 15 vs day 30, p = 0.2099), but does not significantly impair memory performance until day 5 (t-test comparison; day 1, p = 0.6056; day 5, p = 0.0123; day 15, p = 0.0071; day 30, p = 0.0015) and then significantly increases with age. (d) At 27 °C, control flies show a memory decline associated with age that is slightly more pronounced at older ages, and this is significantly increased in flies expressing Aβ42 in the MB neurons (UAS-Aβ42/+; UAS-LacZ/+; ok107-Gal4/+) at all ages tested (t-test comparison; day 1, p < 0.0001; day 5, p < 0.0001; day 15, p = 0.0002; day 30, p < 0.0001). Error bars indicate SEM; n = 10 per group; *p < 0.05, **p < 0.001, ***p < 0.001. (e) Aβ42 immunodetection at day 1, 5 and 15 post-eclosion in protein extracts from flies (UAS-Aβ42/+; ok107-Gal4/+) raised at 25 °C or 27 °C. (f) Aβ42 levels were normalized to the amount of β-Tubulin in the matching groups, observing a correlation between temperature and the level of Aβ42 from day 1 to day 15 (n > 3).
