Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Position of ACE1 R1279Q in human and mouse ACE1.
  • Fig. S2. No changes in renin or angiotensinogen in the brains of ACE1 KI mice.
  • Fig. S3. AngII receptor AT1R is highly expressed in in CA1 and CA2 hippocampal neurons.
  • Fig. S4. ACE1 R1284Q increases ACE1 protein and activity and causes apoptosis in primary neuron culture.
  • Fig. S5. Neurodegeneration and brain atrophy occur selectively in the hippocampus of ACE1 KI mice.
  • Fig. S6. Pyknotic nuclei and activated microglia are present in the brains of ACE1 KI mice.
  • Fig. S7. Female ACE1 KI mice have increased glial markers and reduced synaptophysin compared with male ACE1 KI mice.
  • Fig. S8. EEG and behavioral testing in male ACE1 KI mice.
  • Fig. S9. Positive correlation between hippocampus volume and brain captopril concentration in ACE1 KI mice.
  • Fig. S10. Aβ plaque size and density are unchanged in 5XFAD;ACE1KI/KI mice.
  • Table S1. Whole-genome and whole-exome AD datasets.
  • Table S2. Functional ACE rare variants, showing nominal association (P < 0.05) with AD in at least one of the datasets.
  • Legend for data file S1

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Other Supplementary Material for this manuscript includes the following: