AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBTYPE IMMUNOREACTIVITY IN THE HIPPOCAMPAL-FORMATION OF PATIENTS WITH ALZHEIMERS-DISEASE

Immunocytochemical techniques were employed in order to examine the di stribution and relative intensity of the AMPA receptor subunits GluR1 and GluR2/3 within the hippocampal formation of normal controls and Al zheimer's disease (AD) cases. Throughout our investigation we examined cases exhibiting a wide range of pathologic severity, thus allowing u s to correlate our immunohistochemical data with the extent of patholo gy. Specifically, we investigated the distribution of these receptor s ubunits in hippocampal sectors that are particularly vulnerable to AD pathology (i.e., CA1 and subiculum) and compared these findings with t hose obtained following examination of sectors that are generally resi stant to pathologic change (i.e., CA2/3, dentate gyrus). Within vulner able sectors we observed a variable loss of GluR1 and GluR2/3 immunola beling. The degree to which these proteins were reduced appeared to co rrelate with the extent of neurofibrillary pathology and cell loss. De spite the loss of labeled cells, the intensity of immunolabeling withi n the remaining neurons was comparable with, and in many instances eve n greater than, that observed in control cases. Within resistant secto rs, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increase d in AD cases, particularly in the molecular layer of the dentate gyru s and in the stratum lucidum of CA3 (i.e., the termination zones of pe rforant pathway and messy fibers). In addition, within AD cases dramat ic increases were observed within the supragranular and polymorphic la yer of the dentate gyrus (i.e., the terminal zones of sprouting messy fiber collaterals). The increase in GluR1 and GluR2/3 immunolabeling i s hypothesized to occur in response to the deafferentation of selected glutamatergic pathways. Moreover, our data support that hippocampal p lasticity is preserved, even in severe AD cases, and suggest a critica l role for AMPA receptor subunits in this plasticity and in maintainin g hippocampal functioning. (C) 1995 Wiley-Liss, Inc.