Glutamate

Glutamate is the primary excitatory neurotransmitter in the CNS involved in memory, learning, and neuronal plasticity. It acts by providing information from one brain area to another and affects cognition through facilitation of connections with cholinergic neurons in the cerebral cortex and basal forebrain.18 In AD, one type of glutamate receptor, #-methyl-D-aspartate (NMDA), is less prevalent than normal. There also appears to be overactivation of unregulated glutamate signaling. This results in a rise in calciumions that induces secondary cascades, which lead to neuronal death and an increased production of APP.17 The increased production of APP is associated with higher rates of plaque development and hyperphosphorylation of t protein.19 Memantine is a noncompetitive NMDA antagonist that targets this path-ophysiologic mechanism.20

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