AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBTYPE IMMUNOREACTIVITY IN THE ENTORHINAL CORTEX OF NONDEMENTED ELDERLY AND PATIENTS WITH ALZHEIMERS-DISEASE

The present work employed immunocytochemical techniques and examined t he distribution and cytological features of the AMPA receptor subunits , GluR2/3 and GluR1 within the entorhinal cortex of non-demented elder ly (NC), patients with neuropathological and clinical verification of Alzheimer's disease (AD) and patients without a clinical history of de mentia yet exhibiting sufficient quantities of senile plaques to meet neuropathological criteria of Alzheimer's disease (HPND). In NC cases, GluR2/3-immunolabeled neurons were abundantly distributed throughout layers II, III, V and VI of the entorhinal cortex. In contrast, GluR1- positive cells were comparatively sparse in number and largely restric ted to layers V and VI. In AD, GluR2/3- and GluR1-labeled neurons were markedly reduced. Similarly, adjacent Niss1-stained tissue sections r evealed substantial cell loss in the entorhinal cortex thus providing a reasonable explanation for the loss of these receptor subunits. Impo rtantly, a dramatic loss of GluR2/3- and GluR1-immunolabeled neurons i s also observed in the HPND cases, although examination of Niss1-stain ed tissue sections reveals little if any evidence of cell loss. The la tter data suggest that a 'down-regulation' of these receptor subunits occurs prior to the actual loss of these cells. Furthermore, we hypoth esize that the decrease of specific AMPA receptor subunits may influen ce neuronal vulnerability via a mechanism involving increased intracel lular calcium and the destabilization of intracellular calcium homeost asis.