Variant forms of neuronal glutamate transporter sites in Alzheimer's disease cerebral cortex.
The displacement of Na(+)-dependent D-[3H]-aspartate binding by unlabeled D-aspartate or the inhibitors DL-threo-beta-hydroxyaspartate, L-cysteate, L-glutamate, dihydrokainate, DL-alpha-aminoadipate, alpha-methyl-DL-glutamate, and 1-aminocyclobutane-cis-1,3-dicarboxylate was used to characterize the high-affinity glutamate/aspartate uptake site in human 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 in AD (midtemporal, frontal, caudal cingulate, and hippocampal cortices) were compared with those that are spared (occipital and motor cortices). Profiles of the affinities (Ka values) of the ligands showed that areas spared from damage in AD cases differed significantly from equivalent areas in control (p < 0.001) and DLBD (p < 0.001) cases and also from areas susceptible to damage in the same AD cases (p < 0.001). Areas susceptible to damage in AD showed comparable profiles across the three case groups (p = 0.980). The glutamate/aspartate uptake site may be regionally variant in AD cases, and this may underlie local excitotoxicity. D-[3H]Aspartate binding site density was significantly lower in both dementia groups (control vs. AD, p < 0.001; control vs. DLBD, p = 0.009; but AD vs. DLBD, p = 0.528); within-group differences were not significant (control, p = 0.874; AD, p = 0.285; DLBD, p = 0.741).
Scott
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HL
Royal Brisbane Hospital Foundation, Brisbane, Australia.
Tannenberg
A E
AE
Dodd
P R
PR
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism*; D003544:Cysteic Acid / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D014018:Tissue Distribution; D014316:Tritium
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D005971:Glutamates; D014316:Tritium; C066302:2,4-methanoglutamate; D001224:Aspartic Acid; D018698:Glutamic Acid; D003544:Cysteic Acid