Reduction of adenosine A1-receptors in the perforant pathway terminal zone in Alzheimer hippocampus

The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alzheimer's disease (AD) patients (n = 9) and non-dement controls (n = 3) has been investigated autoradiographically with [H-3]8-cyclopentyl-1,3-dipropylxanthine ([H-3]CPDPX) as the ligand probe. In AD hippocampi binding of [H-3]CPDPX was greatly reduced in the outer two thirds of the dentate gyrus molecular layer, likely due to the degeneration of the perforant path. Binding of [H-3]CPDPX was not significantly altered in other parts of the AD hippocampus, e.g. the CA1 and the CA3, in spite of a pronounced cellular pathology and reduced N-methyl-D-aspartate (NMDA) receptor densities, assessed as strychnine insensitive [H-3]glycine autoradiography. This contrasts with the presumed localization on dendrites of pyramidal neurons of A1 receptors within the CA1 and the CA3.