Association of low plasma Aβ42/Aβ40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease
Association of low plasma Aβ42/Aβ40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease
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DOI：
10.1001/archneur.64.3.354
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发表时间：
2007-03-01
影响因子：
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通讯作者：
Younkin, Steven G.
中科院分区：
文献类型：
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作者：
Graff-Radford, Neill R.;Crook, Julia E.;Younkin, Steven G.
背景：为了开发阿尔茨海默病 (AD) 的预防疗法，必须开发与 AD 相关的生物标志物，以与胆固醇水平识别有心脏病风险的人相同的方式识别高危个体。目的：确定血浆 β 淀粉样蛋白（Aβ 40 和 Aβ42）水平是否有助于识别轻度认知障碍 (MCI) 和 AD 风险增加的认知正常老年白人受试者。设计：使用成熟的夹心酶联免疫吸附测定法，血浆 Aβ 蛋白在前瞻性老年白人队列中对 40 和 A beta 42 水平进行基线分析，随访 2 至 12 年（中位年龄 3.7）年，以检测 MCI 或 AD 的事件病例。 背景：从初级保健机构招募到梅奥·罗切斯特阿尔茨海默病患者登记处的认知正常的社区白人志愿者。患者：我们对 563 名认知正常的白人志愿者（中位年龄 78 岁；62% 女性）进行了随访，他们患有测量基线血浆 Aβ 水平后至少进行 1 次随访。 主要结果指标：主要结果是出现 MCI 或 AD 的时间。次要结果是患者认知变化的年化率，我们对这些患者进行了两次马蒂斯痴呆评定量表评估，间隔 3 至 7 年。 结果：在随访期间，53 名受试者出现 MCI 或 AD。血浆 A beta 42/A beta 40 比率处于下四分位的受试者显示 MCI 或 AD 的风险显着更高（P = .04，根据年龄和载脂蛋白 E 基因型进行调整）。对血浆 A β 42/A β 40 比率处于最低与最高四分位数的受试者进行比较，得出相对风险为 3.1（95% 置信区间，1.1-8.3）。调整年龄和载脂蛋白 E 基因型后，使用痴呆评定量表评分的年化变化作为结果变量进行回归分析，结果显示 A β 42/A β 40 比率较低的参与者认知能力下降幅度更大 (P = 0.02)。结论：血浆 A β 42/A β 40 比率可能是一种有用的病前生物标志物，可用于识别认知正常且罹患 MCI 或 AD 风险增加的老年白人受试者。
Background: 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.Objective: To determine whether plasma levels of amyloid beta protein (A beta 40 and A beta 42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD.Design: Using well-established sandwich enzyme-linked immunosorbent assays, plasma A beta 40 and A beta 42 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.Setting: 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 A beta levels.Main Outcome Measures: 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.Results: During follow-up, 53 subjects developed MCI or AD. Subjects with plasma A beta 42/A beta 40 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 A beta 42/A beta 40 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 A beta 42/A beta 40 ratios had greater cognitive decline (P = .02).Conclusion: The plasma A beta 42/A beta 40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD.