Representative images from a 9-month old epileptic 3×Tg-AD mouse showing colocalization of BACE1-labeled dystrophic neurites with local extracellular Aβ deposits.

<p>The colocalization of Ter42/12F4 and BACE1 IR is illustrated between consecutive sections (<b>A–D</b>) and in double immunofluorescence (<b>E–G</b>). In some large neuritic plaques, the amyloid core (with heavy Aβ IR, arrows) corresponded to a central zone of the neuritic cluster with reduced BACE1 IR (<b>C, D</b>). Note the colocalization of BACE1 IR and 12F4 IR around small as well as large neuritic plaques (<b>E–G</b>). Bar graphs (<b>H–M</b>) quantify the density of BACE1 and Ter42 labeling in temporal regions of epileptic vs control 3×Tg-AD mice. The specific optical density (o.d.) of BACE1 IR measured in CA1 did not significantly change in vehicle-treated mice, but increased from 9 to 14 months of age in the epileptics (<b>H</b>). In the subiculum (<b>I</b>), specific BACE1 o.d. tended to increase from 9 to 14 months of age in both groups, but significantly in the epileptics. Specific BACE1 o.d. in the inner dentate molecular layer did not increase with age in the epileptic mice, but was dramatically higher than controls at all three age points (<b>J</b>). Specific o.d. for Ter42 IR increased in CA1 (<b>K</b>) and subiculum (<b>L</b>) with age in the epileptic mice. No age- or group-related differences in Ter42 IR were found in the inner molecular layer (<b>M</b>). Abbreviations are as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048782#pone-0048782-g001" target="_blank">Figure 1</a>; large arrows bracket mossy fiber sprouting (MFs) in <b>B</b>. Scale bar in (<b>A</b>) = 250 µm for (<b>A, B</b>), 100 µm for (<b>C, D</b>) and 50 µm for (<b>E–G</b>).