J Psychiatry Neurosci 2013; 38(1):6-23
Timothy J. Revett, PhD; Glen B. Baker, PhD, DSc; Jack Jhamandas, MD, PhD; Satyabrata Kar, PhD
Revett, Jhamandas, Kar — Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alta.; Baker, Kar — Department of Psychiatry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alta.
Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.
ubmitted Dec. 8, 2011; Revised Apr. 3, 30, 2012; Accepted May 7, 2012.
Acknowledgements: The authors are grateful to CIHR and the Canada Research Chairs program for their support to the research programs.
Competing interests: None declared for T.J. Revett. G.B. Baker declares educational grant support from Pfizer Canada and travel and speaker fees from the Turkish Association for Psychopharmacology. J.H. Jhamandas and S. Kar are supported in part by a CIHR operating grant paid to their institution.
Contributors: T.J. Revett and S. Kar designed the study. T.J. Revett acquired the data. T.J. Revett, G.B. Baker, J.H. Jhamandas and S. Kar analyzed the data and wrote the article. All authors reviewed the article and approved its publication.
Correspondence to: S. Kar, Centre for Prions and Protein Folding Diseases, Departments of Medicine (Neurology) and Psychiatry, University of Alberta, Edmonton AB T6G 2M8; firstname.lastname@example.org