Differential effects of angiotensin II receptor blockers on Aß generation.

ABSTRACT

Angiotensin II receptor blockers (ARBs) are widely prescribed for the medication of systemic hypertension and congestive heart failure. It has been reported that ARBs can reduce the risk for the onset of Alzheimer's disease (AD) and have beneficial effects on dementia. Neurotoxic amyloid ß-protein (Aß) is believed to play a causative role in the development of AD. However, whether ARBs regulate Aß generation remains largely unknown. Here, we studied the effect of ARBs on Aß generation and found that telmisartan significantly increased Aß40 and Aß42 generation, but decreased the Aß42/Aß40 ratio. However, losartan, valsartan and candesartan did not increase Aß generation, while olmesartan significantly increased Aß42 generation. We also found that telmisartan increased the Aß generation through angiotensin type 1a receptor (AT1a) and the receptor-related phosphotidylinositide 3-kinases (PI3K) pathway. Our findings revealed the different effects of ARBs on Aß generation and provide new evidence for the relationship between antihypertensive treatment and AD pathogenesis.