Figure 5.

Suppression of Fitness-Based Neuronal Selection Decreases Lifespan in a Drosophila Model of AD

(A) GeneSwitch system relies on a chimerical Gal4 containing a steroid receptor domain that only becomes active upon binding the synthetic progesterone analog RU486. This system allows us to induce the conditional expression of the human Aβ42 peptide in the adult brain of elav-GeneSwitch (elavGS) transgenic flies upon addition of RU486 to the food.

(B) Aβ42 (green) expression is detected in the brain of RU486-induced elavGS > Aβ42 flies, but not in the brain of uninduced flies. Aβ42 can form large insoluble aggregates (arrowhead). A posterior view of the brain next to the mushroom body calyx is shown. Actin is in red. Scale bar: 5 μm.

(C) Posterior view of the brain, showing the surrounding region of the mushroom body calyx. Nuclei are marked by DAPI (blue), and actin cytoskeleton is highlighted by phalloidin (red). Degenerative vacuoles are surrounded by a yellow line in grayscale insets. All genotypes were treated with RU486. Scale bar: 10 μm in color pictures or 5 μm in grayscale insets.

(D) Mean number of vacuoles located at a 10-μm-deep plan in 2-week-old brains of the indicated genotypes. Data are represented as mean ± SEM. ^∗∗∗p < 0.001, ^∗∗p < 0.01, ^∗p < 0.05.

(E and F) Lifespan curve (E) and table (F) depicting survival analysis for heterozygous females of the following genotypes: uninduced elavGS > Aβ42 / > lacZ, induced elavGS > Aβ42 / > lacZ, induced elavGS > Aβ42 / > azot RNAi, and induced elavGS > azot RNAi.

See also Figures S4 and S5.