Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study
Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study
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DOI：
10.1212/01.wnl.0000306696.82017.66
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发表时间：
2008-05-06
期刊：
影响因子：
9.9
通讯作者：
DeKosky, S. T.
中科院分区：
文献类型：
--
作者：
Lopez, O. L.;Kuller, L. H.;DeKosky, S. T.
目的：检查心血管健康研究认知研究参与者亚组中正常和轻度认知障碍 (MCI) 受试者的阿尔茨海默病 (AD) 与血浆 A β 1-40 和 A β 1-42 水平之间的关联。方法：我们测定了 274 名非痴呆受试者（232 名）的血浆 A β 1-40 和 A β 1-42 水平。 1998-1999 年，正常值和 MCI 值 42），并在 2002-2003 年重复测量。受试者基线时的平均年龄为 79.3 +/- 3.6 岁。我们检查了随后 4.5 年中 Aβ 水平与 AD 事件之间的关联，控制了年龄、半胱氨酸蛋白酶抑制剂 C 水平（肾小球功能标志物）、载脂蛋白 E-4 等位基因、改良迷你精神状态检查评分和 MRI 识别的梗塞。结果：在正常受试者的未经调整的前瞻性模型中，Aβ1-40 和 Aβ1-42 水平在正常受试者中 1998-1999 年与 2002-2003 年 AD 事件（n = 55）相关（纵向分析）。在完全调整的多变量模型中，A beta 1-42 和 A beta 1-40 及其比率均与 AD 事件无关。然而，调整对 A beta 1-42 的点估计的影响非常小，从未调整模型中的优势比 (OR) 1.61 (p = 0.007) 到完全调整模型中的 OR 1.46 (p = 0.08)。 2002-2003 年（横断面分析），只有未经调整的模型显示这两种肽均与 AD 相关。结论：血浆 A β 水平受年龄以及全身和中枢神经系统血管危险因素的影响。在控制这些条件后，A beta-40 和 A beta 1-42 是正常受试者转化为阿尔茨海默病 (AD) 的弱预测因子，并且在横断面分析中仅与 AD 存在微弱关联。因此，Aβ 的血浆水平似乎并不是 AD 的有用生物标志物。
Objectives: To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study.Methods: We determined the plasma A beta 1-40 and A beta 1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 +/- 3.6 years. We examined the association between A beta levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts.Results: In an unadjusted prospective model in normal subjects, both A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD.Conclusions: Plasma A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of A beta do not seem to be useful biomarkers for AD.