title: The role of the tripartite glutamatergic synapse in the pathophysiology of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.
authors.affiliation: 1Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Rudy
authors.affiliation: 1Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Hunsberger
authors.affiliation: 1Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Weitzner
authors.affiliation: 1Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, WV, 26506, USA ; 2Center for Neuroscience, West Virginia University, Morgantown, WV, 26506, USA ; 3Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Miranda N
authors.initials: MN
authors.lastname: Reed
keywords: Alzheimer’s disease; Beta-amyloid; NMDA; astrocytes; excitotoxicity; glutamate; tau; tripartite synapse
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