摘要：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 (AT 1 R), 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 AT 1 R. However, the precise mechanism underlying how AT 1 R is involved in Aβ production is unknown. Interestingly, AT 1 R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with β 2 -adrenergic receptor (β 2 -AR), which is also shown to be involved in Aβ generation. Therefore, in this study, we aimed to clarify whether the interaction between AT 1 R and β 2 -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 β 2 -AR selective antagonist ICI-118551 more strongly than the treatment of β 1 -AR selective antagonists. Furthermore, deficiency of AT 1 R abolished the effect of β 2 -AR antagonist on the stimulation of Aβ production caused by Telm. Taken together, the interaction between AT 1 R and β 2 -AR is likely to be involved in Aβ production..
