Co-expression of the PolgA D257A mutation and APP/Ld transgene causes morphological features of neurodegeneration. 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 cortical layer V neurons imaged at high magnification by light microscopy. Mouse genotypes are indicated above each column. Representative brain sections from four different mice from each genotype were imaged at 100× magnification. Note that D257A; APP/Ld neurons have abnormal morphologies and display vacuolated nuclei suggestive of marginated chromatin (e.g., black arrows). These features are absent in neurons in D257A, APP/Ld and wild-type brains (scale bar: 50 μm).