Graff-Radford Neill R, Crook Julia E, Lucas John, Boeve Bradley F, Knopman David S, Ivnik Robert J, Smith Glenn E, Younkin Linda H, Petersen Ronald C, Younkin Steven G
Department of Neuroscience, Mayo College of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
Arch Neurol. 2007 Mar;64(3):354-62. doi: 10.1001/archneur.64.3.354.
To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease.
To determine whether plasma levels of amyloid beta protein (Abeta40 and Abeta42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD.
Using well-established sandwich enzyme-linked immunosorbent assays, plasma Abeta40 and Abeta42 levels were analyzed at baseline in a prospective, elderly white cohort followed up for 2 to 12 (median, 3.7) years to detect incident cases of MCI or AD.
Cognitively normal, community-based white volunteers recruited from primary care settings into the Mayo Rochester Alzheimer Disease Patient Registry. Patients We followed up 563 cognitively normal white volunteers (median age, 78 years; 62% female) who had at least 1 follow-up visit after measurement of baseline plasma Abeta levels.
The primary outcome was time to development of MCI or AD. The secondary outcome was the annualized rate of cognitive change in patients for whom we had 2 Mattis Dementia Rating Scale evaluations 3 to 7 years apart.
During follow-up, 53 subjects developed MCI or AD. Subjects with plasma Abeta42/Abeta40 ratios in the lower quartiles showed significantly greater risk of MCI or AD (P = .04, adjusted for age and apolipoprotein E genotype). Comparison of subjects with plasma Abeta42/Abeta40 ratios in the lowest vs the highest quartile gave a relative risk of 3.1 (95% confidence interval, 1.1-8.3). After adjusting for age and apolipoprotein E genotype, regression analysis using annualized changes in the Dementia Rating Scale scores as an outcome variable showed that participants with lower Abeta42/Abeta40 ratios had greater cognitive decline (P = .02).
The plasma Abeta42/Abeta40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD.
为了开发阿尔茨海默病（AD）的预防性治疗方法，开发与AD相关的生物标志物至关重要，这些生物标志物能够像胆固醇水平识别心脏病风险人群那样识别出有风险的个体。
确定血浆β淀粉样蛋白（Aβ40和Aβ42）水平是否有助于识别认知功能正常但患轻度认知障碍（MCI）和AD风险增加的老年白人受试者。
采用成熟的夹心酶联免疫吸附测定法，对一个前瞻性老年白人队列的基线血浆Aβ40和Aβ42水平进行分析，该队列随访2至12年（中位数为3.7年）以检测MCI或AD的发病情况。
从初级保健机构招募认知功能正常、以社区为基础的白人志愿者，纳入梅奥罗切斯特阿尔茨海默病患者登记处。患者：我们对563名认知功能正常的白人志愿者（年龄中位数为78岁；62%为女性）进行了随访，这些志愿者在测量基线血浆Aβ水平后至少有1次随访。
主要观察指标是发生MCI或AD的时间。次要观察指标是在3至7年期间接受2次马蒂斯痴呆评定量表评估的患者的年化认知变化率。
在随访期间，53名受试者发生了MCI或AD。血浆Aβ42/Aβ40比值处于下四分位数的受试者发生MCI或AD的风险显著更高（P = 0.04，经年龄和载脂蛋白E基因型校正）。血浆Aβ42/Aβ40比值处于最低四分位数与最高四分位数的受试者相比，相对风险为3.1（95%置信区间为1.1 - 8.3）。在调整年龄和载脂蛋白E基因型后，以痴呆评定量表分数的年化变化作为结果变量进行回归分析表明，Aβ42/Aβ40比值较低的参与者认知功能下降更明显（P = 0.02）。
血浆Aβ42/Aβ40比值可能是一种有用的病前生物标志物，用于识别认知功能正常但患MCI或AD风险增加的老年白人受试者。
