VARIANT FORMS OF NEURONAL GLUTAMATE TRANSPORTER SITES IN ALZHEIMERS-DISEASE CEREBRAL-CORTEX

The displacement of Na+-dependent D-[H-3]aspartate binding by unlabele d D-aspartate or the inhibitors DL-threo-beta-hydroxyaspartate, L-cyst eate, L-glutamate, dihydrokainate, DL-alpha-aminoadipate, alpha-methyl -DL-gIutamate, and 1-aminocyclobutane-cis-1,3-dicarboxylate was used t o characterize the high-affinity glutamate/aspartate uptake site in hu man cerebral cortex. Synaptosomal membranes were prepared from tissue obtained at autopsy from nondemented control, Alzheimer's disease (AD) , and diffuse Lewy body disease (DLBD) cases, Areas that are damaged i n AD (midtemporal, frontal, caudal cingulate, and hippocampal cortices ) were compared with those that are spared (occipital and motor cortic es), Profiles of the affinities (K-a values) of the ligands showed tha t areas spared from damage in AD cases differed significantly from equ ivalent areas in control (p < 0.001) and DLBD (p < 0.001) cases and al so from areas susceptible to damage in the same AD cases (p < 0.001). Areas susceptible to damage in AD showed comparable profiles across th e three case groups (p = 0.980). The glutamate/aspartate uptake site m ay be regionally variant in AD cases, and this may underlie local exci totoxicity, D-[H-3]Aspartate binding site density was significantly lo wer in both dementia groups (control vs, AD, p ( 0.001; control vs. DL BD, p = 0.009; but AD vs, DLBD, p = 0.528); within-group differences w ere not significant (control, p = 0.874; AD, p = 0.285; DLBD, p = 0.74 1).