Department of Nutrition, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan, 40402, Republic of China.
Metab Brain Dis. 2013 Dec;28(4):597-604. doi: 10.1007/s11011-013-9406-2. Epub 2013 May 4.
Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer's disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n = 32) and Wistar Kyoto (abbreviated WKY; n = 8) rats were divided into 5 groups (each n = 8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aβ-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aβ-42 and hepatic triglyceride concentrations (r(2) = 0.41, p < 0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.
各种流行病学研究表明,2 型糖尿病和代谢综合征与阿尔茨海默病(AD)高度相关。在这里,我们试图评估代谢综合征特征对 AD 进展的影响。将 5 周龄雄性自发性高血压(n = 32)和 Wistar Kyoto(缩写为 WKY;n = 8)大鼠分为 5 组(每组 n = 8):WKY、高血压(HTN)、链脲佐菌素诱导的糖尿病(STZ)、高脂肪饮食(HFD)和 STZ +高脂肪饮食诱导的糖尿病(DM)。所有动物均被处死,采集血液、肝脏和大脑样本进行进一步的生物学分析。在诱导的 15 周期间,STZ 和 DM 组(注射低剂量 STZ 的动物)空腹血糖水平显著升高;HFD 组胰岛素水平升高,但血糖水平正常。HFD 和 DM 组均出现高胆固醇血症和肝甘油三酯和胆固醇水平升高。此外,还观察到 HFD 与脑内淀粉样β 42(Aβ-42)升高、高血糖与脑胰岛素受体下调以及血清 Aβ-42 和肝甘油三酯浓度之间存在相关性(r²=0.41,p<0.05)。血清 C 反应蛋白和丙二醛似乎与 AD 生物标志物的关联没有显著影响。因此,我们的研究表明,具有代谢综合征特征的大鼠具有大量预测 AD 的生物标志物;然而,未发现传统炎症和氧化标志物与 AD 之间存在关系。需要进一步的研究来证明这些在大鼠中的发现与人类 AD 过程有关。