PolgA D257A mutation increases amyloid plaque pathology in APP/Ld mouse brains. (A) Hemi-brains of the same mice from Figure 1 were fixed, sectioned coronally, and co-stained with anti-Aβ42 specific antibody (green) and thiazine red for β-sheet amyloid and imaged by immunofluorescence microscopy. (A) Representative coronal brain sections of APP/Ld (left) and D257A; APP/Ld mice (right). Both APP/Ld and D257A; APP/Ld mice exhibit diffuse (green box) and dense-core (red box) plaques. The insets show high-magnification images of plaques in green and red boxes. Dense-core plaques are positive for both Aβ42 and thiazine red, while diffuse plaques are only Aβ42-immunopositive. In addition to the cortex, D257A; APP/Ld mice form plaques in other brain regions such as the thalamus (for example see red arrow) Blue = DAPI. Scale bar: 500 μm (25 μm in insets). (B) The amyloid plaque density (number of Aβ42-positive plaques per cm2) was determined from representative brain sections with equivalent rostral-caudal location from D257A; APP/Ld (n = 10) and APP/Ld (n = 12) mice. (C) Plaque densities in (B) were normalized to human transgenic APP protein levels as determined by APP immunoblot analysis (Figure 1C). Note that normalized Aβ42 plaque density is significantly increased in D257A; APP/Ld mice compared to APP/Ld mice (mean ± SEM; *p < 0.05; Student’s t-test).