Alterations in adrenergic receptors of frontal cortex and cerebral microvessels in Alzheimer's disease and aging.

Biochemical and pathological abnormalities are evident in the noradrenergic innervation of the cerebral cortex in Alzheimer's Disease (AD), and there is also a decline in aging, which may lead to changes in adrenergic receptors. To assess this question, we analyzed adrenergic receptor subtypes by ligand binding methods in prefrontal cortex and brain microvessels from subjects with AD and aging controls. Ligand binding to adrenoceptors and their subtypes did not change with postmortem delay in obtaining tissues. alpha 1-adrenergic receptors of the frontal cortex did not correlate with age but there was a small (approximately 25%), though significant, reduction in AD subjects. In cerebral microvessels, there were no changes in these receptors. alpha 2-receptors of the cortex significantly declined with age in controls and were also significantly reduced by approximately 50% in AD subjects. However, in cerebral microvessels alpha 2-adrenergic receptors were significantly increased by approximately 60% in AD. We suggest that presynaptic alpha 2-adrenoceptors on noradrenergic synapses may be those that are selectively decreased in the prefrontal cortex in AD. Total beta-receptors in cortex did not correlate with age, nor were they altered in AD. However, beta 1-receptors were decreased but beta 2-receptors were significantly increased in AD, indicating a change in the relative ratio of beta 1/beta 2-receptors. Similarly, beta 2-receptors of cerebral microvessels were significantly increased in AD. These changes suggest receptor "up-regulation" in response to noradrenergic denervation in AD and may reflect functional changes at the blood-brain barrier.