Arthritis exacerbates and accelerates the development of Aβ plaques in mouse brain. (A) Aβ plaques were not observed in the brain of 4 month old APP/PS1 transgenic mice. Conversely, (B) age and gender matched Col1-IL1βXAT;APP/PS1 mice with osteoarthritis presented Aβ-immunoreactive plaques scattered throughout the brain at 4 months of age. At 8 months of age, (C) APP/PS1 mice displayed Aβ plaque deposits throughout the brain parenchyma. (D) Age and gender matched Col1-IL1βXAT;APP/PS1 mice with osteoarthritis presented many more Aβ plaques. Overall, (E) APP/PS1 mice with arthritis displayed a significantly greater number of Aβ plaques at every time point examined (exacerbation effect), as well as developed Aβ plaque deposits the 4 month time point when no plaques were observed in APP/PS1 mice without arthritis (acceleration effect). (F) There was a modest increase in the number of small Aβ plaque deposits (< 100 μm) after osteoarthritis throughout the brain of Col1-IL1βXAT;APP/PS1 mice with osteoarthritis. The number of large Aβ plaques (> 100 μm), however, significantly increased in the mice with osteoarthritis, especially in the middle and posterior thirds of the brain. A total of 38 mice were included in this experiment: 20 Col1-IL1βXAT;APP/PS1 mice with osteoarthritis and 18 APP/PS1 mice without osteoarthritis. Mean ± SEM shown, ***p < 0.001; Bar = 100 μm.