Adrenergic receptors in Alzheimer's disease brain: selective increases in the cerebella of aggressive patients.

In this study, the distribution and concentration of beta1, beta2, and alpha2 adrenergic receptors were examined in the frontal cortex, hypothalamus, and cerebellum of Alzheimer's disease (AD) and age-matched control human brains by receptor autoradiography. The purpose of this study was to detect changes in adrenergic receptor concentrations in key areas of the brain known to affect behavior. For these studies, [125I]iodopindolol ([125I]IPIN) was used to visualize total beta adrenergic sites (with ICI-89,406 and ICI-118, 551 as subtype-selective antagonists to visualize beta2 and beta1 receptors, respectively). [3H]UK-14,304 was used to localize the alpha2 sites. Essentially no significant difference in adrenergic receptor concentration was found between total AD cases taken together and control patients. It was found, however, that there were important distinctions within the AD group when cases were subdivided according to the presence or absence of aggression, agitation, and disruptive behavior. Aggressive AD patients had markedly increased (by approximately 70%) concentrations of alpha2 receptors in the cerebellar cortex compared with nonaggressive patients with similar levels of cognitive deficit. The levels of cerebellar alpha2 receptors in aggressive AD patients were slightly above the healthy elderly controls, suggesting that these receptors are preserved and perhaps increased in this subgroup of AD. beta1 And beta2 adrenergic receptors of the cerebellar cortex showed smaller but significant ( approximately 25%) increases in concentration in aggressive AD subjects versus both nonaggressive AD patients and controls. No significant differences were found in adrenergic receptor concentrations within the frontal cortex or hypothalamus. These results point out the importance of distinguishing behavioral subgroups of AD when looking for specific neurochemical changes. These autoradiographic results may reflect the importance of the cerebellum in behavioral control.