Hippocampal and cortical immunohistochemistry for Na+/K+ ATPase in APP+PS1 mice and non-transgenic littermates. Horizontal hippocampal and cortical sections were immunostained for Na+/K+ ATPase αII. The left panels depict hippocampus, while the right panels encompass the cerebral cortex. Panels A & B: high power magnification (Scale bar = 8.33 μm) revealed membrane-localized staining for Na+/K+ ATPase in the insular cortex (Panel B) and CA3 of the hippocampus (Panel A) of non-transgenic mice. Panel C: hippocampal staining of non-transgenic mice showed a ubiquitous distribution of Na+/K+ ATPase throughout the neuropil, while less staining was apparent along the pyramidal layer of Ammon's horn, the hilus and the granular layer of the dentate gyrus. Panel D: cortical staining was also substantial with slight lightening in layers 1 and 2. White matter in both structures remained unstained. A similar staining pattern was observed in the APP+PS1 mice with the exception of focal non-stained areas in the gray matter, presumably where amyloid plaques are located (Panel E [hippocampus] & F [cortex]). Immunostaining followed by Congo red histochemistry confirmed that the Na+/K+ ATPase staining was absent not only immediately where amyloid was located, but also in a zone surrounding the plaque (Panels G [hippocampus] & H [cortex]). Scale bar for panels C-H = 120 μm.