Abstract: Alzheimer’s disease (AD) constitutes the largest proportion of dementia worldwide, with a significant associated medical burden. The major pathological hallmarks of AD include the gradual accumulation and deposition of amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein (Revett et al., 2013). Whilst investigations centered around the tau and Aβ hypothesis have been the main focus for the previous decades, the lack of therapeutic solutions has pushed for research into other potential therapeutic targets. Pathological alterations in the glutamatergic system have been postulated to play a central role in the pathogenesis of AD, with intimate downstream and upstream interactions with both Aβ and tau protein (Revett et al., 2013; Yeung et al., 2020a, b; Kwakowsky et al., 2021). Aβ1–42 toxicity is mediated in part by N-methyl-D-aspartate receptor (NMDAR) overactivation resulting in elevated intracellular calcium (Ca2+) and subsequent enzyme-induced neuronal death, whilst NMDAR activation has been shown to increase hyper-phosphorylation of neurofibrillary tau (Revett et al., 2013). The complex interrelationship between Aβ1–42, neurofibrillary tau, and the glutamatergic system is still an area of continuing development. A significant disruption of glutamatergic neurons has been well documented in AD, and the subsequent excitatory-inhibitory balance disturbance can potentially contribute to the memory and learning deficits that are characteristic of this condition (Revett et al., 2013; Jurado, 2018; Yeung et al., 2020a, b, 2021; Babaei, 2021; Kwakowsky et al., 2021).