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July 1990

D1-Dopamine Receptor Abnormality in Frontal Cortex Points to a Functional Alteration of Cortical Cell Membranes in Alzheimer's Disease

Author Affiliations

From the Department of Neurology, Academisch Ziekenhuis (Drs De Keyser and Ebinger) and the Protein Chemistry Laboratory (Dr Vauquelin), Vrije Universiteit Brussel, Brussels, Belgium.

Arch Neurol. 1990;47(7):761-763. doi:10.1001/archneur.1990.00530070055011

• 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.