Alzheimer's disease (AD) is a major neurodegenerative disease characterized by a marked decline in the activity of the alpha-ketoglutarate dehydrogenase complex (AKGDHC), a key metabolite of the tricarboxylic acid (TCA) cycle. Earlier studies have shown that the calcium salt of AKG, CaAKG, increases the healthspan and lifespan in C57BL/6 mice by reducing inflammatory cytokines. Here, we demonstrate that CaAKG attenuates long-term potentiation (LTP) in an animal model of AD, APP/PS1 mice. CaAKG application during strong tetanisation converts early-LTP to late-LTP, stable for 4 hours in the CA1 region of hippocampal slices from AD mice. Additionally, we find that CaAKG's effects are more pronounced in females than males, and it facilitates associative memory through synaptic tagging and capture, impacting cognitive processes.In our investigation into the mechanism behind CaAKG's effect on LTP in APP/PS1 mice, we observe that CaAKG improves synaptic plasticity via GluA2-lacking AMPARs, also known as calcium-permeable AMPA receptors (CPAMPARs), and L-type calcium channels. Given the association of dysfunctional autophagy with AD, we explored if CaAKG attenuates synaptic plasticity by enhancing autophagy. Our findings indicate that CaAKG enhances autophagy, supported by increased autophagy markers in hippocampal slices treated with CaAKG. In summary, our study not only highlights the potential of CaAKG to address various aspects of AD pathology, spanning synaptic plasticity to autophagy, but also offers promising avenues for therapeutic interventions in AD.