高血压或增加患阿尔兹海默症的遗传风险

  近日，来自得克萨斯大学的一项最新研究显示，高血压会同遗传风险因素相互作用从而增加患者大脑中淀粉样蛋白（Aβ）的负担；在阿尔兹海默氏症（AD）中，携带载脂蛋白Eε4基因（APOEε4）的个体往往患AD风险较高，而且机体中Aβ的水平较高。甚至在健康受控病人机体中，高血压和APOEε4的存在往往和70岁以上老年个体大脑中Aβ水平升高直接相关。
  尽管APOEε4带来的风险很大，但年龄依然是患AD的最大风险，这就表明年龄相关的并存病或许也很重要，研究者Karen Rodrigue认为，较差的血管健康是老年化人群重要的医学问题；而此前研究也将高血压纳入了其中，来自檀香山亚洲老化研究的一项研究揭示了中年期舒张压、血浆中循环Aβ及个体患AD之间的关系，而另一项研究也显示，弗雷明汉心血管风险评分与较高的淀粉样蛋白负担直接相关。
  在这项研究中，研究者调查了高血压同APOEε4的相互作用对大脑中Aβ积累的影响，利用老年痴呆症神经成像启动计划的研究数据，研究者对1013名年龄在47至89岁之间的多样化人群进行了研究，将研究对象分为控制组（无风险因子个体）、遗传风险组（ε4异质体组或异质体病人）、血管风险组（诊断为高血压或血压较高的病人）或者双风险组（携带遗传风险和血管风险的病人）。
  在所有的参与者中，449名个体（44%）表现出ε4阳性，564名个体（56%）表现出ε4阴性，65%的个体为高血压（平均血压为142/77mm Hg），35%的个体为血压正常者（123/71 mm Hg）；对于所有的参与者而言，APOE基因型的完整数据、正电子发射断层扫描18 F-florbetapir扫描、痴呆症的诊断信息以及高血压状态情况均可以获得。
  18 F-florbetapir扫描结果可以通过标准的摄入值比来表示，也可以通过限制1.1来区分，即结比值高于1.1的被认为Aβ阳性，低于1.1被认为Aβ阴性，扫描结果都是在调整了个体的年龄及体重指数的基础上获得的。（转化医学网360zhyx.com）
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PHILADELPHIA — Hypertension interacts with genetic risk to increase the burden of amyloid beta (Aβ) in the brain, a new study suggests.

In Alzheimer's disease (AD), individuals with the apolipoprotein E (APOE) ε4 gene, indicating higher AD risk, had higher levels of Aβ, researchers report. Even in healthy control patients, the presence of hypertension and APOE ε4-positivity was associated with a greater level of Aβ in the brains of adults older than 70 years.

Despite the strong risk conferred by APOE ε4, age remains the greatest risk factor for AD, suggesting that age-related comorbidities may be important. Among them, "poor vascular health is a significant medical issue in aging populations," Karen Rodrigue, PhD of the Center for Vital Longevity at the University of Texas at Dallas told delegates here at the 7th Clinical Trials on Alzheimer's Disease (CTAD).

Previous studies have implicated hypertension in this process. The Honolulu-Asia Aging Study showed a link between midlife diastolic blood pressure, levels of circulating plasma Aβ, and subsequent probable AD in Japanese-American men who were never treated for hypertension. Another study showed that a higher Framingham cardiovascular risk score correlated with a greater amyloid burden.

In the present study, Dr Rodrigue and colleagues investigated the interaction of hypertension and APOE ε4–positivity on the accumulation of Aβ in the brain.
Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), they studied a cognitively diverse group of 1013 adults aged 47 to 89 years and classified them as a control group (comprising individuals having neither risk factor), a genetic risk group (ε4 heterozygous or homozygous patients), a vascular risk group (patients with a diagnosis of hypertension or elevated blood pressure), or a double risk group (patients with both genetic and vascular risks).

Among the participants, 449 (44%) were ε4-positive, and 564 (56%) were ε4-negative; 65% were hypertensive (average blood pressure, 142/77 mm Hg), and 35% were normotensive (123/71 mm Hg). For all participants, complete data on APOE genotype, positron emission tomography 18F-florbetapir scans, diagnostic information for dementia, and hypertension status were available.

18F-florbetapir scan results were expressed as a standardized uptake value ratio (SUVR, normalized to cerebellar gray matter), and scan results were dichotomized according to a cutoff of 1.1, with ratios greater than 1.1 considered positive for Aβ, after adjustment for age and body mass index.