Changes in β-Adrenergic Receptor Subtypes in Alzheimer-Type Dementia

Authors


Address correspondence and reprint requests to Dr. M. Fujiwara at Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.

Abstract

Abstract: Using ligand binding techniques, we studied β-adrenergic receptor subtypes in brains obtained at autopsy from seven histologically normal controls and seven histopathologically verified cases with Alzheimer-type dementia (ATD). Inhibition of [3H]dihydroalprenolol ([3H]DHA) binding by the selective β, antagonist, metoprolol, results in nonlinear Hofstee plots, suggesting the presence of the two receptor subtypes in the human brain. The calculated ratios of β12-adrenergic receptors in control brains are as follows: frontal cortex, 49:51; temporal cortex, 31:69; hippocampus, 66:34; thalamus, 23:77; putamen, 70:30; caudate, 48:52; nucleus basalis of Meynert (NbM), 43:57; cerebellar hemisphere, 25:75. Compared with the controls, total concentrations of β-adrenergic receptors were significantly reduced only in the thalamus of the ATD brains. β1-Adrener gic receptor concentrations were significantly reduced in the hippocampus and increased in the NbM and cerebellar hemisphere, whereas β2-adrenergic receptor concentrations were significantly reduced in the thalamus, NbM, and cerebellar hemisphere and increased in the hippocampus and putamen of the ATD brains. These results suggest that β1-and β2-adrenergic receptors are present in the human brain and that there are significant changes in both receptor subtypes in selected brain regions in patients with ATD.

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