Loss of glycine-dependent radioligand binding to the receptor complex in patients with Alzheimer's disease

Abstract

Well washed membranes have been prepared from samples of cerebral cortex of control subjects and patients with Alzheimer's disease, obtained both at post mortem and by neurosurgical procedures earlier in the course of the disease. Binding to these membranes of two radioligands for the N-methyl-D-aspartate-phencyclidine receptor complex has been determined in the presence and absence of glycine. Glycine increased the binding in both control and Alzheimer tissue samples. At one concentration of radioligand, in the presence of glycine there was less binding to post-mortem samples, which Scatchard analysis showed was associated with a 36% loss of sites. In rare neurosurgical samples, there was also a loss of binding of radioligand which suggests that the effect is not due to post-mortem artefacts or epiphenomena. These new results may have implications for the symptomatic and preventative treatment of Alzheimer's disease.