Fig. 9

Neuritic degeneration is attenuated in APP_SWE/PS1_dE9 mice overexpressing Prdx6 and exacerbated in Prdx6 haplodeficient mice. a Shown are representative microphotographs of coronal cross-sections through the somatosensory cortex (upper panel) and the dorsal hippocampus (lower panel) from 10-month-old female mice of indicated genotypes, which were stained with Gallyas silver stain. Both the numerical density of neuritic plaques and the number and size of spheroid bodies forming the plaques increase in the rank order of APP/Prd6^Tg < APP/Prd6^+/+ < APP/Prd6^+/−. Arrows indicate mature plaques while arrowheads indicate early stage of neuritic degeneration associated with emerging plaques, which are abundant in the APP/Prd6^−/− mice. b Quantitative analysis of numerical density of Gallyas⁺ neuritic plaques in the brain cortex and in the hippocampus depicted as mean value (+SEM) from n = 6 female mice per genotype. c Shown are high magnification microphotographs of neuritic plaques produced by superimposing bright field picture of silver impregnated spheroids on fluorescent image of X-34 labeled fibrillar plaque core highlighting the differences in plaque composition across the genotypes, which include both the number and the distance spheroid spread away from the fibrillar core. d Representative LCMS images of plaques co-labeled with antibodies against the N-terminus of Aβ peptide (Aβ_1–16) and neurofilaments (NF) from female mice of indicated genotypes demonstrating distorted trajectories of axons passing in the vicinity of the plaques and presence of axonal swellings (spheroids) in the area occupied by anti-Aβ immunolabeling (white encirclement indicated by Aβ plaque mask). Quantification of the number of NF⁺ axonal swellings per Aβ plaque in e and NF⁺ plaque index (NF⁺ % plaque area) in f. Values represent mean (+SEM) from n = 40 randomly selected plaques per genotype. p < 0.001 for the hippocampus in b, and p < 0.0001 for the brain cortex in b, e, and f (ANOVA); *p < 0.05, **p < 0.01, and ****p < 0.0001 (Holm-Sidak’s post-hoc test). Scale bars: 50 μm – the cortex and 200 μm the hippocampus in a, and 10 μm in c and d