Abstract：
Alzheimer\'s disease (AD) has long been considered a brain-specific dementia syndrome. However, in recent decades, the occurrence of cardiovascular (CV) disease in the progression of AD has been confirmed by increasing epidemiological evidence. In this study, we conducted an in-depth cardiovascular characterization of a humanized amyloid precursor protein (APP) overexpressing mouse model (hAPP23+/-), which overexpresses the Swedish mutation (KM670/671NL). At the age of 6 mo, hAPP23+/- mice had a lower survival, lower body weight, and increased corticosterone and VMA levels compared with C57BL/6 littermates. Systolic blood pressure was increased in hAPP23+/- animals compared with C57BL/6 littermates, but diastolic blood pressure was not statistically different. Pulse pressure remained unchanged but abdominal and carotid pulse-wave velocity (aPWV and cPWV) were increased in hAPP23+/- compared with C57BL/6 mice. Echocardiography showed no differences in systolic or diastolic cardiac function. Ex vivo evaluation of vascular function showed decreased adreno receptor dependent vasoconstriction of hAPP23+/- aortic segments, although the isobaric biomechanics of the aortic wall were similar to C57BL/6 aortic segments. In conclusion, hAPP23+/- mice exhibited high serum corticosterone levels, elevated systolic blood pressure, and increased arterial stiffness in vivo. However, ex vivo aortic stiffness of hAPP23+/- aortic segments was not changed and vascular reactivity to α1-adrenoceptor stimulation was attenuated. These findings highlight the need for more frequent assessment of circulating stress hormone levels and PWV measurements in daily clinical practice for people at risk of AD.NEW & NOTEWORTHY We showed that male amyloid precursor protein (APP) transgenic mice have higher circulating stress hormone levels. As a result, higher systolic blood pressure and pulse-wave velocity were measured in vivo in addition to a smaller α-adrenergic receptor-dependent contraction upon ex vivo stimulation with phenylephrine. Our findings highlight the need for more frequent assessment of circulating stress hormone levels and PWV measurements in daily clinical practice for people at risk of Alzheimer\'s disease.
摘要：
阿尔茨海默病(AD)长期以来被认为是脑特异性痴呆综合征。然而,近几十年来,越来越多的流行病学证据证实了AD进展中心血管疾病(CV)的发生.在这项研究中,我们对人源化淀粉样前体蛋白（APP）过表达小鼠模型（hAPP23+/-）进行了深入的心血管表征，过度表达瑞典突变（KM670/671NL）。在6个月的时候，hAPP23+/-小鼠的存活率较低，降低体重，与C57BL/6同窝猫相比，皮质酮和VMA水平升高。与C57BL/6同窝动物相比，hAPP23+/-动物的收缩压升高，但舒张压无统计学差异。与C57BL/6小鼠相比，hAPP23+/-小鼠的脉压保持不变，但腹部和颈动脉脉搏波速度（aPWV和cPWV）增加。超声心动图显示心脏收缩或舒张功能无差异。血管功能的离体评估显示hAPP23+/-主动脉节段的肾上腺素受体依赖性血管收缩减少，尽管主动脉壁的等压生物力学与C57BL/6主动脉节段相似。总之,hAPP23+/-小鼠表现出高血清皮质酮水平，收缩压升高,体内动脉僵硬度增加。然而,hAPP23+/-主动脉节段的离体主动脉硬度没有改变,血管对α1-肾上腺素受体刺激的反应性减弱.这些发现强调了在日常临床实践中需要更频繁地评估处于AD风险的人的循环应激激素水平和PWV测量。NEW&NOTEWORTHY我们表明雄性淀粉样前体蛋白(APP)转基因小鼠具有较高的循环应激激素水平。因此,在体内测量到较高的收缩压和脉搏波速度,此外,在去氧肾上腺素的离体刺激下,α-肾上腺素能受体依赖性收缩较小.我们的研究结果强调，在日常临床实践中，对于有阿尔茨海默病风险的人，需要更频繁地评估循环应激激素水平和PWV测量。
