Structural and functional abnormalities in the cerebral microvasculature have been observed in Alzheimer's disease (AD) patients and animal models. One cause of hypoperfusion is the thickening of the cerebrovascular basement membrane (CVBM) due to increased collagen-IV deposition around capillaries. This study investigated whether these and other alterations in the cerebrovascular system associated with AD can be prevented by long-term dietary supplementation with the antioxidant ubiquinol (Ub) stabilized with Kaneka QH P30 powder containing ascorbic acid (ASC) in a mouse model of advanced AD (3 × Tg-AD mice, 12 months old). Animals were treated from prodromal stages of disease (3 months of age) with standard chow without or with Ub + ASC or ASC-containing vehicle and compared to wild-type (WT) mice. The number of β-amyloid (Aβ) plaques in the hippocampus and entorhinal cortex was higher in female than in male 3 × Tg-AD mice. Extensive regions of hypoxia were characterized by a higher plaque burden in females only. This was abolished by Ub + ASC and, to a lesser extent, by ASC treatment. Irrespective of Aβ burden, increased collagen-IV deposition in the CVBM was observed in both male and female 3 × Tg-AD mice relative to WT animals; this was also abrogated in Ub + ASC- and ASC-treated mice. The chronic inflammation in the hippocampus and oxidative stress in peripheral leukocytes of 3 × Tg-AD mice were likewise reversed by antioxidant treatment. These results provide strong evidence that long-term antioxidant treatment can mitigate plasma oxidative stress, amyloid burden, and hypoxia in the AD brain parenchyma.

在阿尔茨海默氏病（AD）患者和动物模型中已观察到大脑微脉管系统的结构和功能异常。灌注不足的原因之一是由于毛细血管周围胶原IV沉积增加导致脑血管基底膜（CVBM）增厚。这项研究调查了在患有晚期AD的小鼠模型中，通过长期饮食补充抗氧化剂泛醇（Ub）并用含抗坏血酸（ASC）的Kaneka QH P30粉末稳定化，可以预防与AD相关的脑血管系统的这些和其他变化。 （3只Tg-AD小鼠，12个月大）。用无或不含Ub + ASC或含ASC的溶媒的标准饲料治疗疾病前驱阶段（3个月大）的动物，并与野生型（WT）小鼠进行比较。雌性海马和内嗅皮层中的β-淀粉样蛋白（Aβ）斑块的数量高于雄性3×Tg-AD小鼠。缺氧性广泛区域的特征是仅女性具有较高的斑块负担。Ub + ASC废除了这一点，在较小程度上通过ASC处理废除了。不论Aβ负担如何，相对于WT动物，在雄性和雌性3×Tg-AD小鼠中都观察到CVBM中胶原IV沉积的增加。在Ub + ASC和ASC处理的小鼠中也消除了这种情况。3 x Tg-AD小鼠的海马慢性炎症和外周白细胞的氧化应激也可通过抗氧化剂逆转。这些结果提供了有力的证据，表明长期的抗氧化剂治疗可以减轻AD脑实质中的血浆氧化应激，淀粉样蛋白负荷和缺氧。