Genome Wide Association Studies (GWAS) for Alzheimer’s disease (AD) have identified a number of genes that are significantly associated with the disease (van der Kant et al., 2019). We use the genetic tractability and short lifespan of Drosophila to make and characterise novel sporadic AD models based on these candidate AD risk loci. We have obtained transgenic RNAi lines for the closest Drosophila homologue for each of these ~20 candidate genes which will be screened in fruit flies for AD relevant phenotypes. Firstly, RNAi will be expressed in all neurons (using elav-GAL4) or all glia (using repo-GAL4) and the effect on lifespan measured (normally 1-2 months) using longevity assays and survival curve analysis as well as in the eye (using GMR-GAL4) to assess degeneration, all assays set up in the lab (Higham et al., 2019b; Lowe et al., 2019). Secondarily, changes in memory will be assessed with the olfactory-shock conditioning assay by expressing the RNAi in the fly’s memory neurons, the mushroom body (with OK107-Gal4) using assays routinely used in the lab to assess the effect of AD on memory (Higham et al., 2019a; Higham et al., 2019b). Thirdly, the effect of the AD risk gene knock down on circadian rhythms and sleep will be assessed by expressing the candidates in all clock neuron (with Tim-Gal4) or pan-neuronally respectively using assays routinely used in the lab to measure the effect of AD on circadian rhythms and sleep (Buhl et al., 2019).
School of Physiology, Pharmacology and Neuroscience