Increased alpha 2- and beta 2-adrenergic receptors in cerebral microvessels in Alzheimer disease

Adrenergic receptors exist in brain microvessels which are innervated by noradrenergic locus ceruleus neurons. Biochemical and pathological studies indicate locus ceruleus degeneration in Alzheimer disease (AD), which can cause adrenergic receptor alterations in brain microvessels. To assess this, we studied adrenergic receptors in human brain microvessels from AD subjects and age-matched controls by ligand binding methods. Total beta receptors of cerebral microvessels and beta 2 receptors, the type which predominates in microvessels, were significantly increased in AD. Compared to the cerebral cortex, there was a paucity of alpha 1-adrenergic receptors in cerebral microvessels, and they did not change in AD. Binding to alpha 2 receptors in cerebral microvessels was approximately 50% of that in the cortex, and these receptors increased by approximately 60% in cerebral microvessels of AD subjects. These findings suggest adrenergic receptor 'upregulation' in response to noradrenergic deafferentation in AD, which may have functional consequences at the blood-brain barrier.