Staging of Alzheimer's Pathology in Triple Transgenic Mice: A Light and Electron Microscopic Analysis

Figure 3

Photomicrographs showing 6E10 intraneuronal immnostaining in the cortex ((a)–(c)), ventral CA1 ((d)–(f)), BLA ((g)–(i)), and subiculum ((j)–(o)) in 3-week, 9- and 20-month-old 3xTg-AD mice. Round-or oval-shaped 6E10-ir neurons were found at the youngest age in all brain regions examined independent of fixation ((a), (d), (g)). At 9 months some 6E10 stained neurons appeared shrunken with a hollow center ((b), (e), (h)). 6E10 immunopositive plaques were found throughout the subiculum of female (j), and to a lesser extent in male mutant mice (m) at 20 months of age. Solid and dashed boxed areas in panels (j) and (m) outline a 6E10-ir plaque (k) and CA1-ir neurons shown at higher magnification in (l) and (o), respectively. Dashed line in panel m demarks the CA1 field from the subiculum. Higher-power photomicorgraph shows a posterior subicular 6E10 positive plaque in a female 20-month-old mutant mouse (n). Tissue processed following 6E10 antibody peptide preadsorbtion shows a lack of intra-or extraneuronal staining in CA1 or subiculum (P). Note the more diffuse compared to the compact nature of plaques found in male-versus female-aged mutant mice. Ntg mice failed to display 6E10 immunoreactivity (c, f, i) at 3 weeks of age. Scale bar in ((a)–(i)); ((k), ((l), (n), (o)) = 20 𝜇m, ((j), (m)) = 100 𝜇m.