Changes in Adrenergic and Cholinergic Receptors on Human Cerebral Vessels

Background/Objectives: Sporadic cerebral amyloid angiopathy (CAA) occurs due to a failure of clearance of amyloid-beta (Aβ) along the walls of capillaries and arteries. Soluble Aβ is eliminated from the brain along the basement membranes of capillaries and arteries as Intramural Periarterial Drainage (IPAD). The motive force for IPAD is provided by the spontaneous contractions of vascular smooth muscle cells, as vasomotion. Cerebrovascular smooth muscle cells receive adrenergic and cholinergic innervation from the Locus Coeruleus and the Nucleus Basalis of Meynert, which are compromised very early in Alzheimer’s disease (AD). Here, we tested the hypothesis that adrenergic and cholinergic receptors are histologically preserved in parenchymal and leptomeningeal blood vessels with CAA. Methods: Using immunohistochemistry, we examined the cerebrovascular distribution of muscarinic (M1, M2), nicotinic (α 7 nicotinic acetylcholine receptor), and adrenergic (α1b/2b) receptors in post-mortem brain tissue. We compared receptor distribution across CAA and non-CAA patients, as well as young and old patients without CAA. Results: We found significant differences in the receptor immunoreactivity of α7 nicotinic acetylcholine receptors, as well as α1b and α2b adrenergic receptors. However, there were no differences in the receptor immunoreactivity of M1 or M2 muscarinic receptors between patient groups. Conclusions: As IPAD depends on the functionality of the vascular smooth muscle cells to maintain the integrity of IPAD with aging, based on these histological findings, future therapeutic interventions could focus on agonists of α7 nicotinic acetylcholine and α1b/2b adrenergic receptors.