Amyloid beta (ABeta) and tau protein are both implicated in memory impairment in early Alzheimer’s disease, but whether and how they interact to cause synaptic dysfunction are unknown. Consequently, I firstly investigated whether tau protein is required for the robust phenomenon of ABeta-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. I demonstrate that the absence of tau prevents the ABeta-induced impairment of LTP; moreover, a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks both an ABeta-induced increase in tau phosphorylation and the ABeta-induced LTP impairment. Thus, tau protein, likely in its phosphorylated form, is required for ABeta to impair LTP. Secondly, I investigated the underlying mechanisms for this ABeta-induced impairment and find that ABeta changes the balance between the two major types of glutamate receptors involved in plasticity processes, with a specific effect on GluN2B subunit-containing NMDA receptors. Since the distribution of these receptors is asymmetric between the left and right mouse hippocampus, I accessed these different types of synapses optogenetically and found that only the GluN2B-rich synapses receiving left CA3 input show ABeta-induced changes in the balance of glutamate receptors, suggesting an asymmetry in synaptic vulnerability to ABeta. Moreover, there was a left-right difference in tetanus-induced LTP and therefore, thirdly, I investigated whether mice have a hemispheric dissociation in memory processing using acute optogenetic silencing of left or right CA3 during hippocampus-dependent memory tasks. Unilateral silencing of either the left or the right CA3 caused a deficit in short-term memory, but only left CA3 silencing impaired performance on a spatial long-term memory task. Together, these results suggest that memory may be routed via distinct left-right pathways within the mouse hippocampus, and that neural pathways subserving distinct functions may also be differentially vulnerable to pathological changes at the synaptic level.