DIFFERENTIAL ALTERATIONS IN ADENOSINE-A(1) AND KAPPA-1-OPIOID RECEPTORS IN THE STRIATUM IN ALZHEIMERS-DISEASE

The alterations in Alzheimer's disease (AD) of two binding sites in th e striatum suggested to have a presynaptic localisation have been inve stigated by quantitative ligand binding autoradiography. Adenosine Al binding sites labelled with [H-3]cyclohexyladenosine (CHA) and kappa1 opioid binding sites labelled with [H-3]U-69593 were studied in adjace nt sections of the striatum obtained postmortem from 10 patients with AD and 9 matched controls. In AD, there was a significant reduction of [H-3]CHA binding sites in the caudate nucleus (control = 88 +/- 4; AD = 56 +/- 6 pmol/g tissue; mean +/- S1.E.MX.) and putamen (control = 8 3 +/- 4; AD = 58 +/- 7 pmol/g). In control subjects, highest levels of [H-3]U-69593 binding were localised to patches within the caudate nuc leus (9.66 +/- 0.58 pmol/g) with lower levels in the matrix (5.54 +/- 0.48 pmol/g). There was no alteration in [H-3]U-69593 binding sites in either the caudate nucleus (patches and matrix) or putamen of AD pati ents. The activity of choline acetyltransferase (ChAT), determined in the same tissue samples used for autoradiographic analysis, was signif icantly reduced in AD (control = 124 +/- 11; AD = 64 +/- 14 nmol/h/mg protein). There was a positive correlation between ChAT activity and [ H-3]CHA binding (r = 0.769), but not [H-3]U-69593 binding (r = 0.197). The results indicate that a marked loss of adenosine A1 receptors occ urs in the striatum of AD with no IOSS Of kappa1 opioid receptors, and that the loss of A1 receptors parallels the loss of choline acetyltra nsferase activity.