Alzheimer’s disease (AD) is characterized by accumulation of amyloid-beta (Aβ) in amyloid plaques and transgenic and knock-in mice that express mutant alleles of amyloid precursor protein (APP) have been used to model the effects of Aβ. This study examined visual system plasticity in transgenic mice that express and secrete Aβ throughout the brain in the absence of APP overexpression to explore the effects of elevated expression of Aβ on synaptic function in vivo. Transgenic mice that express either Aβ40 or Aβ42 were investigated for their ability to appropriately demonstrate ocular dominance plasticity following monocular deprivation. Cortical responses to visual stimulation were assessed using optical imaging of intrinsic signals and Arc immediate early gene expression. Plasticity impairment was demonstrated in mice expressing either Aβ40 or Aβ42, suggesting either species is capable of impairing plasticity when overexpressed. The dataset includes in situ hybridization and optical imaging data.