AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBTYPE IMMUNOREACTIVITY IN THE HIPPOCAMPAL DENTATE GYRUS OF PATIENTS WITH ALZHEIMER-DISEASE - EVIDENCE FOR HIPPOCAMPAL PLASTICITY

Immunocytochemical techniques were employed in order to examine the di stribution and relative intensity of immunolabeling of the lpha-amino- 3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptor subunits GluR1 and GluR2/3 within the hippocampal formation of patients with Alzheim er disease (AD). Within sectors of the hippocampus that are particular ly vulnerable to AD pathology (i.e., CA1, subiculum), we observed a va riable loss of GluR1 and GluR2/3 immunolabeling correlating with the e xtent of cell loss and neurofibrillary pathology. In contrast, in less vulnerable sectors of the hippocampus (i.e., CA2/3, dentate gyrus), t he intensity of immunolabeling was markedly increased in AD cases, par ticularly in the molecular and polymorphic layers of the dentate gyrus . Importantly, these latter regions correspond to termination zones of glutamatergic perforant pathway axons and messy fiber collaterals, re spectively. The increase in immunolabeling within these projection fie lds is hypothesized to occur in response to the deafferentation of sel ected glutamatergic pathways, and suggests a critical role for AMPA re ceptor subunits in hippocampal plasticity.