Hippocampal excitatory amino acid receptors in elderly, normal individuals and those with Alzheimer's disease: non-N-methyl-D-aspartate receptors.

Quantitative receptor autoradiography was used to examine the density and distribution of 3H]kainic acid and 3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites in the hippocampal formation and parahippocampal gyrus obtained at autopsy from 10 Alzheimer's disease and eight normal control individuals. In control and Alzheimer's disease individuals, 3H]kainic acid saturation binding analysis in the outer molecular layer of the dentate gyrus fitted a single-site model. Added calcium ions did not alter the density of 3H]kainic acid binding in the human tissues. These results suggest that calcium-sensitive high-affinity kainic acid binding sites are not present in the human brain in contrast to kainic acid receptors in the rat brain. 3H]AMPA binding was also slightly different in the human brain as compared to the rat, being greatest in the inner third as compared to the outer two-thirds of the dentate gyrus molecular layer. In both control and Alzheimer's disease individuals, 3H]kainic acid and 3H]AMPA binding densities were similar at anterior and posterior levels of the hippocampal formation. In Alzheimer's disease patients, there was a significant increase in 3H]AMPA binding in the infragranular layer. In some, but not all Alzheimer's disease patients, there was an increase in 3H]kainic acid binding densities in the outer half of the dentate gyrus molecular layer. The same individuals which exhibited an increase in 3H]kainic acid binding in the outer molecular layer also displayed increased 3H]AMPA binding in the hilar region. Similar alterations in 3H]kainic acid binding have been observed in rats which had received fimbria-fornix lesions, a model of chronic epilepsy and in individuals with temporal lobe epilepsy. Advanced Alzheimer's disease patients are at risk of developing seizures. The results suggest that several factors including cortical and subcortical pathology and seizure activity may contribute to the alterations in 3H]kainic acid and 3H]AMPA binding observed in the hippocampal formation in Alzheimer's disease.