The Glutamatergic System in Alzheimer's Disease

Glutamate-mediated neurotoxicity has been implicated in the pathogenesis of Alzheimer’s disease (AD). Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system (CNS) and is involved in almost all CNS functions. It signals through a variety of ionotropic and metabotropic receptors. NMDA receptors are ligand-gated cationic channels that are composed of NR1 subunits combined with NR2 (A-D) or NR3 (A-B) subunits. The glutamatergic hypothesis postulates that the progressive cognitive decline seen in AD patients is due to neuronal cell death caused by over activation of NMDA receptors and the subsequent pathological increase in intracellular calcium. Research has shown that both soluble Amyloid beta oligomers and Tau can interact with several glutamate signaling proteins, such as NMDA receptors and proteins involved in glutamate uptake and recycling, leading to glutamate excitotoxicity. Several current AD treatments target glutamatergic signaling including memantine, which is a FDA-approved low-affinity NMDA receptor antagonist. R&D Systems offers a range of research tools needed for investigating the role of the glutamatergic system in AD.