Glutamate system, amyloid ß peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology.
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 ß 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 ß and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid ß production, but also amyloid ß 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.
Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada.
Timothy J
TJ
Revett
Glen B
GB
Baker
Jack
J
Jhamandas
Satyabrata
S
Kar
D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D013570:Synaptic Membranes / Q000378:metabolism / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D016875:tau Proteins; D018698:Glutamic Acid; D008559:Memantine