Mice

5xFAD mice overexpressing human APP and PSEN1 with AD-associated mutations were obtained from the NIH mutant mouse research and resource center (MMRCC). These mice were bred with Aqp4^−/− mice on a C57Bl/6 background that were previously generated in our laboratory [32]. Offspring were genotyped for APP and PSEN1 (which co-segregated as expected) and for Aqp4. F1 offspring that were heterozygous at all 3 loci (5xFAD^+/−; Aqp4^+/−) were then interbred and F2 offspring were genotyped as before. F2 offspring that were heterozygous for APP and PSEN1 and either wild-type or homozygous negative for Aqp4 (5xFAD^+/−; Aqp4^+/+ or 5xFAD^+/−; Aqp4^−/−) were maintained until 7–9 months of age and then sacrificed by transcardial perfusion with 4% formaldehyde and the brain was processed for paraffin embedding. All procedures were approved by the UCSF Institutional Animal Care and Use Committee. A total of 5 Aqp4^−/− 5xFAD mice and 8 wild-type littermates were used in this study.