Co-expression of the PolgA D257A mutation and APP/Ld transgene causes brain atrophy. (A) Coronal sections (30 μm) of brains from D257A; APP/Ld, D257A, APP/Ld, and wild type mice were selected from similar rostral-caudal positions, stained with hematoxylin and imaged by light microscopy. Mouse genotypes are indicated above the micrographs. High magnification images of cortical regions dorsal to the hippocampus (boxed areas) are presented to the right of each low magnification image. Note that the brains of D257A; APP/Ld mice are significantly smaller in size compared to the other genotypes. Especially noticeable is the reduced cortical thickness of D257A; APP/Ld mice. (scale bar = 250 μm for high magnification, 2 mm for low magnification). (B) Lateral cortical thickness (μm) was measured as the length of a line (drawn in the wild-type high magnification image in (A)) running perpendicular to the cortical layers from the dorsal edge of the CA1 region of the hippocampus to the visible boundary of the cortex. The brains of D257A; APP/Ld mice show significant thinning of the cortex compared to the other genotypes (n = 5; mean ± SEM; *p < 0.05; One-way ANOVA followed by Newman–Keuls multiple-comparisons post hoc test). (C) Hippocampal area (μm2) of the different genotypes was also measured. Note that D257A; APP/Ld mice also exhibit significantly reduced hippocampal area compared to APP/Ld, D257A or wild-type mice (n = 5; mean ± SEM; **p < 0.01; ***p < 0.001; One-way ANOVA followed by Newman–Keuls multiple-comparisons post hoc test).