Hippocampal adenosine A1 receptors are decreased in Alzheimer's disease

Previous studies showed that adenosine receptors of the temporal and frontal cortices were not affected in Alzheimer's disease (AD). Here, we assessed the specific binding of [3H]cyclohexyladenosine to adenosine1 (A1) receptors in hippocampus from AD subjects and age-matched controls. By both particulate membrane and in vitro autoradiographic receptor binding methods we demonstrate that A1 receptors are significantly reduced by 40-60% in AD subjects. Scatchard analysis showed that maximum binding capacity (Bmax) was affected and there was no evidence for a change in the affinity of the receptor for the ligand (Kd). Receptor autoradiography revealed that although several regions including CA1, CA3 and deep layer of the subiculum were affected, the loss in A1 receptors was most prominent in the molecular layer of the dentate gyrus. In view of previous evidence indicating that these receptors are associated with the perforant pathway and dendritic fields of the CA1 and CA3 regions, our findings suggest loss of the presynaptic A1 receptors on axon terminals of extrinsic pathways including the perforant path and intrinsic pyramidal neurons which release glutamate.