Density and pharmacology of alpha 5 subunit-containing GABA(A) receptors are preserved in hippocampus of Alzheimer's disease patients

The anatomical localization and pharmacology of alpha 5 subunit-containing GABA type-A receptors in the human hippocampal formation of Alzheimer's dis ease patients were studied with an alpha 5 receptor selective ligand, [H-3] L-655,708 and compared to age-matched human controls. Autoradiographic anal yses revealed a heterogeneous distribution of [H-3]L-655,708 binding sites in CA1-CA3 areas with high levels in stratum oriens, stratum pyramidale and stratum radiatum contrasting with low levels in stratum lacunosum. The hig hest quantity of alpha 5 receptors was found in the molecular layer of the dentate gyrus. This pattern of expression was identical in both hippocampus from control and Alzheimer's disease subjects. Quantitative studies demons trated that the number of [H-3]L-655,708 binding sites is well preserved in Alzheimer's disease with only a moderate reduction (25-30%) in the CA1 sub field and entorhinal cortex. Furthermore, saturation and competition experi ments with [H-3]L-655,708 and representative benzodiazepine site ligands re vealed that alpha 5 receptors in Alzheimer's hippocampus have an alpha 5 be ta 2/3 gamma 2 pharmacology and structure as in control human brain. Overall, the data reported here provide evidence for a specific expression and relative sparing of alpha 5 subunit-containing gamma-aminobutyric acid type-A receptors in the hippocampus of Alzheimer's patients. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.