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The Glutamatergic System and Alzheimer’s Disease

Therapeutic Implications

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Abstract

Alzheimer’s disease affects nearly 5 million Americans currently and, as a result of the baby boomer cohort, is predicted to affect 14 million Americans and 22 million persons totally worldwide in just a few decades. Alzheimer’s disease is present in nearly half of individuals aged 85 years.

The main symptom of Alzheimer’s disease is a gradual loss of cognitive function. Glutamatergic neurotransmission, an important process in learning and memory, is severely disrupted in patients with Alzheimer’s disease. Loss of glutamatergic function in Alzheimer’s disease may be related to the increase in oxidative stress associated with the amyloid β-peptide that is found in the brains of individuals who have the disease. Therefore, therapeutic strategies directed at the glutamatergic system may hold promise. Therapies addressing oxidative stress induced by hyperactivity of glutamate receptors include supplementation with estrogen and antioxidants such as tocopherol (vitamin E) and acetylcysteine (N-acetylcysteine). Therapy for hypoactivity of glutamate receptors is aimed at inducing the NMDA receptor with glycine and cycloserine (D-cycloserine). Recently, memantine, an NMDA receptor antagonist that addresses the hyperactivity of these receptors, has been approved in some countries for use in Alzheimer’s disease.

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Acknowledgements

This work was supported in part by grants from the National Institutes of Health (AG-10836; AG-05119). The authors have no conflicts of interest with regard to the contents of this manuscript.

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  1. Department of Chemistry, Center of Membrane Sciences and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, 40506-0055, USA

    D. Allan Butterfield & Chava B. Pocernich

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  1. D. Allan Butterfield
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  2. Chava B. Pocernich
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Correspondence to D. Allan Butterfield.

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Butterfield, D.A., Pocernich, C.B. The Glutamatergic System and Alzheimer’s Disease. CNS Drugs 17, 641–652 (2003). https://doi.org/10.2165/00023210-200317090-00004

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