Figure 3.

Concentration-dependent induction of cerebral β-amyloidosis by intraperitoneal seeding with Aβ-containing brain extract in APP23 mice. A, Tg extract and PBS dilutions 1:10 and 1:100 thereof (200 μl) were intraperitoneally injected into young 1- to 2-month-old APP23 mice. Control mice were inoculated with 200 μl of brain extract from non-Tg WT mice (WT extract). The last group received a Tg extract that was mixed with the anti-Aβ-specific antibody β1 before the injection. All mice were males. Brains were immunohistochemically analyzed for Aβ deposition 8 months after intraperitoneal injection. Shown are representative coronal sections (scale bar, 500 μm), and higher-magnification images of the frontal cortex are shown below (scale bar, 100 μm). The undiluted Tg extract induced the expected Aβ deposition (see also Fig. 1B). The 1:10 diluted Tg extract induced appreciable amyloid deposition, whereas the 1:100 diluted Tg extract did no longer induce noticeable Aβ deposits (the same was true for the 1:1000 dilution; data not shown) and was identical to the WT extract-injected mice. Amyloid deposition in mice that received the extract/β1 mixture was markedly reduced. Note that some endogenous Aβ plaques are typical for 9- to 10-month-old APP23 mice (age at analysis). B, Stereological quantification of neocortical Aβ load, n = 3–4 mice per group; for the analysis, the 1:100 and 1:1000 dilutions were combined; mean ± SEM is indicated). C, Neocortical Aβ load was differentiated into vascular and parenchymal deposits. Although the majority of Aβ deposits induced by the undiluted Tg extract were detected in the brain parenchyma, deposition induced by the 1:10 diluted Tg extract showed prominent percentage of vascular deposits. D, Neocortical amyloid load was differentiated in congophilic (Congo red positive) and non-congophilic Aβ deposits revealing that the induced Aβ deposits are primarily of a diffuse nature. (However, note that Congo red stains only the core of a plaque and thus the area fraction is low compared with the Aβ stain of a given amyloid plaque.) The increased percentage of Congo red staining in the 1:100 dilution group represents the endogenous Aβ plaques. nctx, Neocortex; undil, undiluted.