D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer's disease
J. De Keyser, G. Ebinger and G. Vauquelin
Department of Neurology, Academisch Ziekenhuis, Brussels, Belgium.
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.
