beta 40

Aims: Alzheimer's disease (AD) is characterized by vascular dysfunction, in addition to memory impairment. Previously we found that beta-sheet breaker peptides (beta SBPs) improved memory impairment induced by amyloid beta-peptide A beta 40. In this study we investigated beta SBP effects on vascular responses in a rat model of AD.Main methods: AD model was induced by bilateral injection of aged A beta 40 (3 nmol) into the amygdala. beta SBPs 15-22, 16-23 and 17-24 (30 nmol) were injected into the amygdala 8 days after A beta 40. The A beta 40 deposits were examined immunohistochemically in cerebral vessels and thoracic aorta. The effects on high-K+ contractility, phenylephrine (PE) contractility, acetylcholine (ACh) relaxation and sodium nitroprusside (SNP) relaxation were investigated in isolated thoracic aorta. Nitric oxide (NO) level in serum was investigated 14 days after A beta 40.Key findings: A beta 40 was localized and it induced vascular damage in minute and small perforating cerebral vascular endothelium, and tunica intima (endothelial) and media (smooth muscle cells) of the thoracic aorta. In intact aorta, ACh-relaxation was decreased by A beta 40, an effect reduced by beta SBPs 15-22 and 16-23. In denuded aorta. A beta 40 decreased PE-contractility. beta SBP15-22 increased ACh-relaxation, whereas beta SBP17-24 increased K+-contraction. A beta 40 decreased NO, an effect inhibited by the beta SBP15-22.Significance: These results provide evidence that A beta 40-perverted endothelium-dependent relaxation and decreased serum NO in AD rats were improved differentially by the beta SBP15-22. These results show the ability of A beta 40 to alter vascular responses. beta SBPs appear to be promising candidate for prevention of these consequences and therapy of AD. (C) 2013 Elsevier Inc. All rights reserved