Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.
Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the number of neurofibrillary tangles as revealed by Congo red staining of adjacent sections. All assays and measurements were done by observers blinded to the clinical diagnoses. Binding was decreased significantly for all ligands except quisqualate in stratum pyramidale of CA1 of the Alzheimer's disease brains. The binding loss was significantly greater for the non-quisqualate and NMDA sites than for the muscarinic, benzodiazepine and kainate sites with the total glutamate and PCP site losses being intermediate. Only the loss of benzodiazepine binding was significantly correlated with the number of neurofibrillary tangles. Lesser binding losses were seen in adjacent areas. This difference in the degree of binding decrease is consistent with the hypothesis that NMDA receptors are located on more distal dendrites of hippocampal neurons. There they may be relatively more vulnerable than the other receptors to the pathological process.
Penney
J B
JB
Department of Neurology, University of Michigan, Ann Arbor 48104.
Maragos
W F
WF
Greenamyre
J T
JT
Debowey
D L
DL
Hollingsworth
Z
Z
Young
A B
AB
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D005971:Glutamates / Q000032:analysis; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000032:analysis; D010622:Phencyclidine / Q000032:analysis; D011963:Receptors, GABA-A / Q000032:analysis; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D011976:Receptors, Muscarinic / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D017478:Receptors, Phencyclidine; D012044:Regression Analysis
D005971:Glutamates; D007608:Kainic Acid; D010622:Phencyclidine; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine