To create an animal model of AD that more accurately reflects disease progression across different genetic backgrounds, we combined 2 previously published fly models that model the downstream pathology in both EOAD and LOAD—Aβ42 accumulation and hyperphosphorylation of tau [Supplementary Fig. 1 (Wittmann et al. 2001; Finelli et al. 2004)]—with a model of natural genetic variation, the Drosophila Genetic Reference Panel (DGRP) (Mackay et al. 2012). Here, MAPT is linked to Alzheimer disease.