Single immune challenge in adults induces a dramatic increase in Aβ plaque burden and prominent neurodegeneration in 3xTg-AD mice. Representative images of (A-B) immunoperoxidase labeling, (C-H) immunofluorescence, and (I-K) silver staining of coronal brain sections of 15-month-old 3xTg-AD mice (Tg) exposed to polyriboinosinic-polyribocytidilic acid (PolyI:C) or NaCI (NaCl) at 4 months of age. (A-B) The typical anti-Aβ1–16 IR seen in the NaCI-treated mice was significantly aggravated after PolyI:C exposure. (C-D) Counterstaining revealed newly formed Aβ plaques in subiculum and CA1 (arrows) that were thioflavinS (ThioS)-negative, suggesting the non-fibrillary nature of the immune challenge-induced plaques. (E-H) Representative images of the ventral CA1 area of (E, F) NaCI-treated and (G,H) PolyI:C-treated transgenic animals, highlighting the striking increase in ThioS-negative Aβ plaques after a single immune challenge. (I-K) The increased plaque deposition in PolyI:C-treated 3xTg-AD mice was accompanied by distinct neurodegeneration. Note the dark precipitates in the vicinity of large plaques in PolyI:C treated mice. (J,K) Higher-magnification color image acquired in the marked area in (J) showing the dense silver precipitates, indicative of dystrophic neurites (red arrows), surrounding Aβ plaques (gray/yellow). Abbreviations: so, stratum oriens; sr, stratum radiatum; slm, stratum lacunosum moleculare; Sub, subiculum; DG, dentate gyrus. (A) = 500 μm; (C) = 150 μm; (E; K) = 50 μm; (I) = 100 μm.