Interaction between Angiotensin Receptor and β-Adrenergic Receptor Regulates the Production of Amyloid β-Protein.

Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid β-protein (Aβ) within the parenchyma of the brain. Aβ is considered to be the key pathogenic factor of AD. Recently, we showed that Angiotensin II type 1 receptor (AT₁R), which regulates blood pressure, is involved in Aβ production, and that telmisartan (Telm), which is an angiotensin II receptor blocker (ARB), increased Aβ production via AT₁R. However, the precise mechanism underlying how AT₁R is involved in Aβ production is unknown. Interestingly, AT₁R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with β₂-adrenergic receptor (β₂-AR), which is also shown to be involved in Aβ generation. Therefore, in this study, we aimed to clarify whether the interaction between AT₁R and β₂-AR is involved in the regulation of Aβ production. To address this, we analyzed whether the increase in Aβ production by Telm treatment is affected by β-AR antagonist using fibroblasts overexpressing amyloid precursor protein (APP). We found that the increase in Aβ production by Telm treatment was decreased by the treatment of β₂-AR selective antagonist ICI-118551 more strongly than the treatment of β₁-AR selective antagonists. Furthermore, deficiency of AT₁R abolished the effect of β₂-AR antagonist on the stimulation of Aβ production caused by Telm. Taken together, the interaction between AT₁R and β₂-AR is likely to be involved in Aβ production.

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