The role of the N-methyl-D-aspartate receptor in Alzheimer’s disease: Therapeutic potential

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with an unknown etiology. Pathologic processes implicated in AD include β-amyloid-induced synaptic failure; tau hyperphosphorylation; inflammation; oxidative stress; abnormal neurotransmission involving acetylcholine, glutamate, norepinephrine, serotonin, and dopamine; and abnormalities in second messengers, protein kinases, and apoptosis. Although each of these pathways offers potential therapeutic targets, pharmacologic manipulation of the glutamatergic N-methyl-D-aspartate receptor pathway, alone or in combination with cholinergic therapies, is emerging as the next promising strategy for the treatment of AD and vascular dementia.