Extended Data Fig. 9: Structural characterization and comparison of ex vivo Aβ42 fibrils after incubating with AV-45.
From: Unraveling Alzheimer’s complexity with a distinct Aβ42 fibril type and specific AV-45 binding
a., b. Representative cryo-EM micrographs of AD1 soluble Type I (a) and Type III (b) fibrils incubated with AV-45. Insets: 2D class averages. c Cross-section of density maps from previously reported ex vivo Aβ42 fibrils extracted from the brains of sporadic AD patients by sarkosyl-based extraction method (top, EMD-ID: EMD-13800) and water-based soaking method (bottom, EMD- ID: EMD-15770). Potential solvent densities in the AV-45 binding channel are indicated in red arrow heads. d Structural comparison between the soluble Type I fibrils of AD1 with and without the addition of AV-45. One half of structural model is shown in sticks, and the other half is shown by main chains. R.m.s.d. between these two structures is 0.305 over 64 Cα atoms (global alignments).e., f. Cross-section view of the Type III:AV-45 complex density map (e) and the structural model fitted in the density map within 2-Å radius of the model (f). Extra densities are colored in orange. g. Structural comparison between the Type III fibrils of AD1 with and without the addition of AV-45. The r.m.s.d. between the two structures is 0.527 over 80 Cα atoms (global alignments).
