REDUCTION OF AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBUNITS IN THE ENTORHINAL CORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE PATHOLOGY - A BIOCHEMICAL-STUDY

Using biochemical techniques we determined concentrations of the AMPA- selective glutamate receptor subunits GluR1 and GluR2/3 in the entorhi nal cortex of patients with Alzheimer's disease pathology and age-matc hed controls. Tangle density was also determined in anatomically match ed samples and correlated with GluR1 and GluR2/3 receptor concentratio n. In Alzheimer's disease brain, Western blot analysis revealed averag e reductions of 43% and 38% for GluR1 and GluR2/3, respectively. Based on previous immunohistochemical studies, we infer that the majority o f protein reduction was due to decreases in GluR1 and GluR2/3 immunola beled elements in the more superficial layers of the entorhinal cortex (layers II and III). These layers of the entorhinal cortex contained numerous neurofibrillary tangles in Alzheimer's disease, but neither G luR1 nor GluR2/3 protein concentration correlated significantly with t angle density. We hypothesize that the decrease in specific glutamate receptor subunits, particularly GluR2/3, may contribute to the vulnera bility of neurons in the entorhinal cortex via mechanisms involving ca lcium conductance through AMPA-selective channels.