Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Representative kymographs for BACE1-mCherry and GFP-GGA3 cotransport experiments in Fig. 2D.
  • Fig. S2. Representative images for PI analysis in Fig. 3B.
  • Fig. S3. Colocalization analysis for BACE1-mCherry with EEA1 and LAMP2.
  • Fig. S4. Representative image for BACE1-mCherry and LAMP2 in Gga3−/− axonal swelling.
  • Fig. S5. NFH staining of hippocampal CA1 axonal bundles and BACE1 accumulation in the cerebellum and hippocampus of Gga3−/− mice.
  • Fig. S6. Images for BACE1-mcherry and GFP-GGA3 channels corresponding to axon in Fig. 6A.
  • Fig. S7. Supplementary data and analysis related to BACE inhibition experiments.
  • Fig. S8. Representative images of cerebella and hippocampi from MBi-3–treated mice.
  • Fig. S9. Images for BACE1-mcherry and GFP-GGA3 channels corresponding to axons in Fig. 7C.
  • Table S1. [MBi-3] micromolars—Pharmacokinetics (PK) analysis summary.
  • Table S2. Genetics dataset description.
  • Table S3. Selected single variants, showing nominal association with AD in one of the datasets.
  • Table S4. Summary of the antibodies used throughout this study.
  • Legend for data file S1
  • References (6064)

[Download PDF]

Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.mp4 format). BACE1-mCherry and GFP-GGA3 axonal trafficking in wild-type neurons.
  • Movie S2 (.mp4 format). BACE1-mCherry and synaptophysin-GFP axonal trafficking in Gga3+/+ and Gga3−/− neurons.
  • Movie S3 (.mov format). Three-dimensional reconstruction of BACE1-mCherry and LAMP2 in Gga3−/− axonal swelling.
  • Movie S4 (.mp4 format). BACE1-mCherry and synaptophysin-GFP accumulation in axonal swellings in Gga3−/− neurons.
  • Movie S5 (.mp4 format). Representative movies for BACE1-mCherry trafficking experiments in Fig. 6.
  • Movie S6 (.mp4 format). Representative movies for BACE1-mCherry trafficking experiments in Fig. 7.
  • Data file S1. Individual-level data file n < 20 (provided as separate Excel file).