AMPA/kainate receptor gene expression in normal and Alzheimer's disease hippocampus

Alzheimer's disease is a progressive dementia characterized by pronounced degeneration of certain populations of neurons in the hippocampus and cerebral cortex of the brain. One theory is that glutamate receptor-mediated toxicity plays a role in cell loss associated with Alzheimer's disease. We used in situ hybridization to examine GluR1, GluR2, and GluR3 messengerRNAs (encoding alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptor subunits) in sections of autopsy samples of Alzheimer's disease brains and age-, sex-, and post-mortem delay-matched brains from non-demented (control) subjects. GluR1 and GluR2 exhibited a heterogeneous distribution in control brain. GluR1 was expressed in granule cells of the dentate gyrus, in pyramidal cells of the CA1 and CA3 hippocampal subfields and in neurons of the subiculum and entorhinal cortex. GluR2 mRNA was at high density in the dentate gyrus and in CA3, but was at low density in CA1, subiculum, and entorhinal cortex. GluR3 hybridization was at very low levels but selectively localized to the dentate gyrus and CA3. In cerebellum, GluR1 was found in granule and Purkinje cell layers. In sections from Alzheimer's disease brain, a high degree of intersubject variability was observed: some samples showed markedly reduced GluR1 mRNA levels in dentate gyrus, CA1 and CA3 relative to controls; others showed no changes. Microscopic observation of emulsion-dipped sections revealed that the reduction of GluR1 seen in the dentate gyrus and CA3 of some Alzheimer's disease subjects was not due to cell loss.(ABSTRACT TRUNCATED AT 250 WORDS)