Fig. 3
From: Aβ43 aggregates exhibit enhanced prion-like seeding activity in mice
Increased cerebral Aβ42 levels in mice inoculated with recombinant Aβ43 aggregates. a Schematic of the intracerebral inoculation procedure in AppNL−F mice and the experimental timeline. b Formic acid-extractable Aβ42 levels (mean ± s.e.m.), as determined by Aβx-42 ELISA, in brains from AppNL−F mice at 6 months post-inoculation with recombinant Aβ aggregates (n = 6, 8, 10, or 8 for Aβ38, Aβ40, Aβ42, and Aβ43, respectively) or purified brain-derived Aβ aggregates from either TgCRND8 (n = 9) or AppNL−F (n = 9) mice. Aβ42 levels in mice inoculated with either dH2O (n = 5) or material derived from a non-Tg mouse brain subjected to the Aβ purification protocol (n = 6) are also shown. Levels of Aβ42 were significantly higher in mice injected with recombinant Aβ43 aggregates or brain-derived Aβ aggregates compared to mice injected with dH2O (P = 0.0061 for Aβ43, P = 0.018 for TgCRND8, and P = 0.021 for AppNL−F as determined by a Kruskal–Wallis test followed by Dunn’s multiple comparisons test; all other groups are non-significant compared to dH2O-injected mice). c Levels of formic acid-extractable full-length total Aβ (mean ± s.e.m.), as determined by Aβ1-x ELISA, in brains from AppNL−F mice inoculated with either dH2O (n = 3), Aβ38 (n = 6), Aβ40 (n = 7), Aβ42 (n = 10), Aβ43 (n = 8), TgCRND8 Aβ (n = 9), or AppNL−F Aβ (n = 9). Levels of total Aβ were significantly higher in mice injected with recombinant Aβ43 aggregates or brain-derived Aβ aggregates compared to mice injected with dH2O (P = 0.010 for Aβ43, P = 0.023 for TgCRND8, and P = 0.045 for AppNL−F as determined by a Kruskal–Wallis test followed by Dunn’s multiple comparisons test; all other groups non-significant compared to dH2O-injected mice). d Soluble Aβ42 levels (mean ± s.e.m.), as determined by Aβx-42 ELISA, in brains from AppNL−F mice inoculated with recombinant Aβ42 aggregates (n = 8), recombinant Aβ43 aggregates (n = 8), TgCRND8 Aβ aggregates (n = 8), or AppNL−F Aβ aggregates (n = 9). Levels of soluble Aβ42 were significantly higher in mice injected with recombinant Aβ43 aggregates or brain-derived Aβ aggregates compared to mice injected with recombinant Aβ42 aggregates (P = 0.025 for Aβ43, P = 0.039 for TgCRND8, and P = 0.0039 for AppNL−F as determined by a Kruskal–Wallis test followed by Dunn’s multiple comparisons test). In panels b-d, open circles indicate female mice and filled circles indicate male mice