Figure 9.

Abnormal morphologies are prevented by overexpression of CaN inhibitory peptide AKAP79 in APP/PS1 mouse brain. A1, In vivo low-magnification image of GFP-expressing neurites and axons (green), blood vessels containing Texas Red, and amyloid deposition stained with methoxy-XO₄ (blue). Arrows indicated Aβ deposits. A2, A3, High-magnification live images taken from ∼100 μm below the brain surface in the neocortex of adult APP/PS1 mice show dendritic spines and dystrophies in both vector- and AKAP79-expressing conditions. B–D, Quantification of spine density (B), dendritic dystrophies (C), and neurite curvature (D) near Aβ deposits in vector- or AKAP79-expressing APP/PS1 mouse brain shows that AKAP79 expression decreases dystrophy size (B; vector, 16.4 ± 6.1 μm²; AKAP79, 12.8 ± 3.6; p = 0.029; n = 45 from 4 animals), increases spine density (C; vector, 17.8 ± 3.0/100 μm; AKAP79, 28.3 ± 6.1; p < 0.001; n > 400 spines), and decreases abnormal neurite curvature near plaques (D) (n = 4 animals for each condition and total > 400 spines). E, Postmortem sections indicated axonal dystrophies with SMI312 staining (red) and plaques with thioflavin S (blue) shows that plaque-associated axonal dystrophies are reduced (quantified in F; vector, 16.4 ± 6.1 μm²; AKAP79, 12.8 ± 3.6; p = 0.0291; n = 45 plaques from 4 animals) in areas injected with AKAP79. F, Quantification of numbers of axonal dystrophies per single Aβ deposits from postmortem sections. Values represent mean ± SD. *p < 0.05; **p < 0.01.