Establishment of a Drosophila AD model

Alzheimer’s disease (AD) is the most common form of dementia that affects people’s health greatly. Though amyloid precursor protein (APP) has been implicated in the pathogenesis of AD, the exact role of APP and its underlying mechanism in AD progression have remained largely elusive. Drosophila melanogaster has been extensively used as a model organism to study a wide range of human diseases including AD. In this protocol, we expressed full length human APP in the Drosophila nervous system and examined its effect on locomotion and choice ability. We found that expression of APP produced locomotion defects in larvae as measured by plate crawling ability assay (PCA), and in adult flies as monitored by plate cycling ability assay (CLA). In addition, expression of APP results in male courtship choice (MCC) defect, since wild-type males court preferentially toward young virgin females over old ones, while APP-expressing males failed to show this preference. This protocol enables us to screen for novel AD candidate genes as well as therapeutic compounds to ameliorate the disease.