Glutamate and Alzheimer's disease

Aim. To analyze the importance of the neurotransmitter glutamate in the pathogenesis of Alzheimer's disease (AD). Development. Elements of the physiological glutamatergic neurotransmission are reviewed, such as the neuronal types that utilize it, glutamatergic receptors and their characteristics, and glutamate transporters that remove this amino acid from the synaptic cleft. Some aspects of AD neuropathology changes in the brain content of glutamate, and other changes in the different types of glutamatergic receptors and transporters are also examined. A mechanism of disease related to prolonged exposure to glutamate, known as 'slow or indirect excitotoxicity', peculiar to some neurodegenerative diseases, is analyzed, as are the causes that may unleash it in AD. Some of the neuropathologic findings in this disease may be related to the glutamatergic dysfunction. Conclusion. Glutamatergic dysfunction plays an important role in the pathogenesis of this illness, although this disturbance is probably a secondary phenomenon to other neurochemical, genetic or metabolic changes, essential to the development of AD.