Figure 3.

Drosophila models of AD and assays for neurodegeneration. (a) Drosophila models of AD. The GAL4/UAS system is routinely used in Drosophila to drive expression of a gene of interest [12]. There are ubiquitous or tissue-specific enhancers that drive expression of GAL4. By crossing lines containing the driver-GAL4 to the UAS-gene of interest, the progeny will result in ectopic expression. Eye, neuronal, glial, or ubiquitous drivers are used to express Aβ or APP and BACE1 transgenes resulting in specific phenotypes. These can be assessed for neural degeneration and dysfunction. (b) Assays to assess neuronal dysfunction. Using the eye-specific driver GMR-GAL4, APP + BACE1 can be expressed during eye development and the adult eye disruption can be observed. The degenerative eye shows disruption of ommatidial structure, reduced size, and loss of pigmentation. This is a useful system to screen for modifiers of APP + BACE1 toxicity. Lifespan analyses can be performed using neuronal, glial, or ubiquitous cell type driver lines and the effect of genetic modifiers on the longevity of APP + BACE1 flies can also be monitored. Climbing assays can be used to examine locomotor deficits that are known to degenerate with age. Flies are tapped to the bottom of a measuring cylinder and the number of flies that can climb above a certain height is recorded. Also relevant for studies in AD are assays for learning and memory such as odour preference teamed with an electrical shock treatment.