To create an in vivo multicellular model system suitable for investigating a functional link between Tip60 HAT activity and APP in neuronal function in vivo, we generated transgenic flies expressing either our previously characterized HAT-defective dominant negative Tip60 transgene (dTIP60E431Q) or additional copies of wild-type Tip60 transgene (dTip60WT) in a well characterized AD fly model [25], [26] that overexpresses either full-length human APP (APP) or human APP lacking the Tip60-interacting C-terminal domain (APP dCT) under the control of the UAS promoter. This evidence concerns the gene KAT5 and Alzheimer disease.