Pre- and Postsynaptic Cortical Glutamatergic Binding Sites in Alzheimer’s Disease
The distribution and density of Na+-dependent glutamate uptake sites and glutamate receptor subtypes; kainate, quisqualate and N-methyl-d-aspartate (NMDA), were measured in adjacent sections of frontal and temporal cortex obtained postmortem from six patients with Alzheimer’s disease (AD) and six age-matched controls. Binding of [3H]-d-aspartate to Na+-dependent uptake sites was reduced by approximately 40% throughout AD frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]-Kainate receptor binding was significantly increased in deep layers of AD frontal cortex compared to controls, but unaltered in superficial laminae. There was a positive correlation (r=0.914) between kainate binding and senile plaque numbers in deep cortical layers. NMDA-sensitive [3H]-glutamate binding was slightly reduced (25%) only in superficial layers of AD frontal cortex relative to controls, but was unrelated to senile plaque numbers in these laminae (r=0.104). Quisqualate receptors, as assessed by [3H]-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]-AMPA) binding, were unaltered in AD frontal cortex compared to controls. There were no significant alterations in preor postsynaptic glutamatergic sites in AD temporal cortex relative to control subjects.
These results indicate that alterations in glutamatergic transmission occur in specific regions of the cerebral cortex in AD and that, in the presence of cortical glutamatergic terminal loss, plastic alterations are evident in some glutamate receptor subtypes but not in others.
KeywordsKainate Receptor Cortical Pyramidal Neuron Superficial Lamina AMPA Binding Glutamate Receptor Subtype
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