Ringman John M, Elashoff David, Geschwind Daniel H, Welsh Brian T, Gylys Karen H, Lee Cathy, Cummings Jeffrey L, Cole Greg M
Mary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, 10911 Weyburn Ave, Ste 200, Los Angeles, CA 90095, USA.
Arch Neurol. 2012 Jun;69(6):757-64. doi: 10.1001/archneurol.2012.277.
To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels.
Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays.
A tertiary referral dementia research center.
Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years.
Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models.
Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins.
We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life.
研究家族性阿尔茨海默病（FAD）突变和载脂蛋白E（APOE）基因型对血浆信号蛋白水平的影响。
采用多重免疫分析法对77种蛋白质的血浆水平进行横断面比较。
一家三级转诊痴呆研究中心。
来自携带早老素1（PSEN1）或淀粉样前体蛋白（APP）突变家族的33人，年龄在19至59岁之间。
使用多元线性回归模型比较FAD突变携带者（MCs）和非携带者（NCs）之间以及APOE基因型组之间的蛋白质水平。
21名参与者为FAD MCs，12名为NCs。6人具有APOE ε2/3基因型，6人具有ε3/4基因型，21人具有ε3/3基因型。17种蛋白质的水平在APOE基因型组之间存在差异，12种蛋白质在年龄和APOE基因型之间存在显著交互作用。ε2携带者中载脂蛋白E和超氧化物歧化酶1的血浆水平最高，ε4携带者中最低，ε3携带者中处于中间水平。多种白细胞介素的水平呈现相反的模式，在ε4携带者中，与年龄呈显著负相关。虽然FAD MCs和NCs之间没有显著差异，但13种蛋白质在突变状态和APOE基因型之间存在交互作用。
我们在APOE基因型组的中青年人群中发现了不同的炎症标志物模式。APOE ε4携带者的载脂蛋白E水平最低。年轻的ε4携带者炎症标志物增加，且随年龄增长而减少。我们证明了ε4携带者在中青年期炎症反应发生改变，这可能与晚年患阿尔茨海默病的风险有关。
