Figure 2.
Propagation of Aβ morphotypes by seeding. Brain extracts from aged amyloid-depositing APP23 or APPPS1 mice were injected into the hippocampus (dentate gyrus) of APP23 or APPPS1 mice. APP23 mice were 4–6 months old when they were injected. They were analysed 3 months later (n=5/extract). APPPS1 mice were either 1.5–2 months or 3 months old when they were injected. The 1.5–2-month-old group was analysed 1.5–2 months later (n=6/extract). The 3-month-old group was analysed 3 months later (n=2/extract). (A) Pattern of induced Aβ-deposition (Aβ immunostaining) in the dentate gyrus. Shown is an APPPS1 extract-inoculated APPPS1 host. (B–E) Higher magnifications of Aβ-immunostained layers of the dentate gyrus for the four experimental groups. The APP23 extract-induced Aβ deposits in APP23 hosts are more diffuse and filamentous compared with the highly coarse, punctate and compact Aβ deposits in APPPS1 extract-induced APP23 hosts (B,C). The distribution of the induced Aβ deposits throughout the different layers was also different between the two extracts in the APP23 host (sgl=subgranular cell layer; g=granular cell layer; iml, oml=inner and outer molecular layer). In the APPPS1 host, the APP23 extract-induced Aβ-deposits also appeared somewhat more diffuse and filamentous compared with the APPPS1 extract-induced Aβ-deposits, whereas the APPPS1 extract induced again more prominent Aβ-deposition in the sgl compared with the APP23 extract (D,E). Overall, the morphological differences between the two extracts in the APPPS1 host were less obvious than in the APP23 host and this appeared true independent of the age of the host at the time of inoculation and of the inoculation period. Note that untreated APP23 mice at 7–9 months of age do not yet show endogenous Aβ plaques in the hippocampus whereas APPPS1 mice at 4–6 months of age occasionally have some endogenous hippocampal plaques, which however can easily be identified (arrowhead in E). Total Aβ load (grey bars) and compact Aβ load (black bars) in dentate gyrus is shown in the panels next to the histological panels. Mean and s.e.m. are indicated (for the APP23 host n=5/extract, for the APPPS1 host n=8/extract). ANOVA (extract × host) for the Aβ load revealed a significant interaction F(1.22)=6.19; P<0.05 and a significant main effect for extract (F(1.22) =7.78; P<0.05) but not for host (P>0.05). ANOVA for the compact Aβ revealed a significant main effect for host (F(1.22) =10.12; P<0.01) but not for extract or interaction (P>0.05). (F–I) tPTAA stained dentate gyrus for the four experimental groups. Note the difference in colour between the APP23 extract-induced Aβ deposits (yellow–greenish, F) and the APPPS1 extract-induced Aβ deposits (yellow–reddish, G) in APP23 hosts. The difference between the two extract in the APPPS1 host was again somewhat less prominent (H, I). Scale bars, 200 μm (A), 100 μm (E) and 50 μm (I). Aβ, β-amyloid peptide; ANOVA, analysis of variance; tPTAA, trimeric polythiophene acetic acid.
