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• W2073666445 abstract "Alzheimer's disease (AD) is one of the most common causes of cognitive impairment, and impairs social interaction and the quality of life for patients. Recently, management of blood pressure with antihypertensive drugs is reported to be effective for prevention of cognitive deficit; however, little is known about the effects of these drugs on AD. Telmisartan, an angiotensin II type1 (AT1) receptor blocker (ARB), is an unique antihypertensive agent with an agonistic action of peroxisome proliferator-activated receptor gamma (PPARγ). Activation of PPARγ has been reported to induce clearance of Aβ peptide and repression of β-secretase; therefore, PPARγ agonists have been expected for the prevention and possible treatment of AD. Here, we investigated the preventive effects of telmisartan on cognitive impairment in AD model mice. Male 8-week-old ddY mice were used for this study. Non-hypotensive dose of telmisartan and GW9662, a PPARγ antagonist, were administered in drinking water. Aβ1-40 was intracerebroventricularly injected 2 weeks after drug treatment. After 4 weeks of Aβ injection, cognitive function was evaluated by passive avoidance test and the Morris water maze. Expressions of mRNA in the brain were analyzed by real-time RT-PCR method. Regional cerebral blood flow was measured by two-dimensional blood blow meter. Concentration of Aβ in the brain was determined by ELISA. Immunohistochemical staining was used for detection of Aβ deposition in the brain. In both cognitive tests, Aβ-injection significantly impaired learning ability. However, pretreatment with telmisartan improved such cognitive decline to the control level. Moreover, pretreatment with telmisartan significantly enhanced cerebral blood flow and suppressed the mRNA expression of proinflammatory cytokine, TNF-α in the brain. Concentration and deposition of Aβ in the brain was markedly reduced by pretreatment with telmisartan. Interestingly, coadministration with GW9662 markedly decreased these beneficial effects of telmisartan. Treatment with GW9662 alone did not affect these parameters. Moreover, ARB without PPARγ antagonist showed less effect. These finding suggest that telmisartan has a preventive effects on cognitive decline in AD mouse model, at least in part due to possible synergistic PPARγ activation and AT1 receptor blockade, which would enhance-clearance of Aβ peptide and anti-inflammatory effects." @default.
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• W2073666445 date "2010-07-01" @default.
• W2073666445 modified "2023-09-27" @default.
• W2073666445 title "P3-271: Telmisartan, an angiotensin II receptor blocker, ameliorates cognitive impairment induced by amyloid beta injection partly due to partial agonistic activation of PPAR-gamma" @default.
• W2073666445 doi "https://doi.org/10.1016/j.jalz.2010.05.1771" @default.
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