D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer's disease.

D1-dopamine receptors and their high-agonist affinity (RH) sites were determined in postmortem-obtained frontal cortex from seven patients with histopathologically confirmed Alzheimer's disease and from seven controls matched for sex, age, and postmortem delay. Total D1-dopamine receptor concentration was unchanged in patients with Alzheimer's disease compared with controls, but the RH sites were significantly reduced in number. Since the RH sites are thought to represent a conformational change of the receptors, induced by the interaction of agonist-bound receptor with a signal transduction protein located in the cell membrane, the reduced ratio of RH sites to total receptors suggests a functional alteration of cortical cell membranes in Alzheimer's disease. Such a cell membrane abnormality might explain why substitution therapy in Alzheimer's disease has been largely disappointing.