Characterization of [125I]HEAT binding to alpha 1-receptors in human brain: assessment in aging and Alzheimer's disease.

The binding of [125I]2-(beta-4-hydroxyphenylethylamino-ethyltetralone ([ 125I]HEAT), an alpha 1-adrenergic receptor antagonist, to human brain membranes was characterized and the binding assessed in tissue from subjects with Alzheimer's disease (AD) and aging controls. Under Na+-K+ phosphate buffer conditions, [125I]HEAT bound to a single class of binding sites in prefrontal cortex (Brodmann area 10) with a Kd of about 120 pM. High binding capacities of [125I]HEAT were evident in the hippocampus and neocortex but were low in subcortical areas and cerebral microvessels comparable to the regional distribution of [3H]prazosin binding reported previously. Displacement of [125I]HEAT by various adrenergic drugs was consistent with its binding to alpha 1-adrenergic receptors. The specific binding was not affected by postmortem delay between death and freezing of tissue at autopsy. There was no correlation of [125I]HEAT binding with age of subjects. In AD subjects, the binding was significantly decreased in prefrontal cortex by about 25% but not changed in hippocampus, putamen or cerebellum compared to age-matched controls. The reduced binding of [125I]HEAT in prefrontal cortex may reflect a region-specific change in alpha 1-adrenergic receptors associated with neuronal loss in AD.