Figure 1

Increased unrepaired DNA damage in hippocampus in young and aged APP/PSEN1 mice. (a) β-amyloid plaques were detectable in low numbers, and small sizes in young APP/PSEN1 mice, but percent coverage increased significantly in older mice (t(9) = 4.80, p < 0.001). (b) Total neuron number (NeuN-positive cells) in hippocampus was lower in young APP/PSEN1 mice (red squares) compared to wild-type (WT, open circles) litter-mates (t(7) = 2.865, p = 0.024). (c) Apoptosis, as measured by percent Caspase 3-positive neurons was elevated in APP/PSEN1 mice hippocampus at both ages (t(7) = 9.52, p < 0.001; t(4) = 5.57, p = 0.0051). (d) Persistent DNA damage (γ-H2AX-staining of DSB) increased in the APP/PSEN1 mice at both ages (t(8) = 6.79, p < 0.0001; t(4) = 3.672, p = 0.0213). Markers of DNA repair via (e) the homologous recombination directed repair pathway (HDR, Rad51, t(4) = 3.667, p = 0.0215) but not through, (f) the non-homologous end-joining pathway (NHEJ, 53BP1) were decreased in APP/PSEN1 mice at both time points. (c–f). Number of stain-positive caspase 3, and the foci of H2AX and 53BP1 were calculated as a percent of Neu-N positive cells, except for RAD51 which are calculated based on area. Data were analyzed by two-tailed t-test between genotypes, within each age group. *P < 0.025, **P < 0.01, ***P < 0.001 different from wild-types as marked. β-amyloid plaque coverage is shown as difference between ages in APP/PSEN1 mice only ***P < 0.001. All images are taken from dentate gyrus in young mice. Images taken at 10X, with inset taken at 40X magnification, except for (a) which were imaged at 4X.