Extended Data Figure 5: Accumulation of CTF-η in dystrophic neurites.

a, Immunohistological stainings of cortical sections of 6-month-old APPPS1-21 transgenic mice (n = 3) revealed 6E10-positive amyloid-β plaque cores (encircled) surrounded by dystrophic neurites positive for 2E9 (white arrowheads, top) and 9476M (white arrowheads, middle). Y188 (bottom panel) staining co-localized with 2E9-positive signal (yellow arrowheads, bottom). Nuclei were counterstained with DAPI. Scale bar, 10 μm. b, Accumulation of CTF-η fragment in dystrophic neurites of 14-month and 24-month-old APPPS1-21 mice. Western blot analysis of material obtained by LCM of APPPS1-21 brain sections (n = 5) bearing thioflavin-S-positive amyloid-β plaque core (P) and the surrounding amyloid-β plaque halo (H). As a control (C), brain areas devoid of plaques were used. While amyloid-β was readily detected by antibody 2D8 in lysates containing plaque-enriched material and halo regions (fractions P and H; bottom), CTF-η was selectively detected in the lysates prepared from the region enriched in dystrophic neurites (H; top), but not detected in plaque or control regions (P or C). As expected, CTF-β/α species are also enriched in dystrophic neurites (H).