Assessment of Racial Disparities in Biomarkers for Alzheimer Disease
Assessment of Racial Disparities in Biomarkers for Alzheimer Disease
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DOI：
10.1001/jamaneurol.2018.4249
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发表时间：
2019-03-01
期刊：
影响因子：
29
通讯作者：
Xiong, Chengjie
中科院分区：
文献类型：
--
作者：
Morris, John C.;Schindler, Suzanne E.;Xiong, Chengjie
阿尔茨海默病分子生物学标志物的种族差异可能提示种族依赖的生物学机制。目的确定阿尔茨海默病分子生物学标志物是否存在种族差异。设计、地点和对象（173名非裔美国人）从2004年1月1日至2015年12月31日入组，在华盛顿大学的奈特阿尔茨海默病研究中心进行了纵向研究，并完成了对大脑和/或大脑的磁共振成像研究。或用匹兹堡化合物B（聚集的淀粉样蛋白β的放射性配体）对脑进行正电子发射断层扫描和/或对淀粉样蛋白β 42、总tau和磷酸化tau 181的浓度进行脑脊液（CSF）测定。从2016年4月22日至2018年8月27日，对每种生物标志物模式进行了独立的横断面分析，并进行了方差分析或协方差分析，包括年龄、性别、教育水平、种族、载脂蛋白E（APOE）β 4等位基因状态和临床状态（正常认知或痴呆）。所有生物标志物的评估都是在不了解参与者临床状态的情况下进行的。主要结果和测量主要结果是根据颅内体积差异调整的海马体积，转换为标准化摄取值比率的全球脑淀粉样蛋白负荷（部分体积校正）和淀粉样蛋白β 42，总tau，结果1255名受试者中，（707名妇女和548名男子;平均[SD]年龄，70.8 [9.9]岁），173名非裔美国人参与者中有116名（67.1%）和1082名非西班牙裔白色参与者中有724名（66.9%）认知正常。在脑磁共振成像结果、匹兹堡化合物B的平均皮质标准化摄取值比值或CSF中淀粉样蛋白β 42浓度上观察到的脑缺血性病变频率无种族差异。然而，在有痴呆家族史的个体中，非裔美国人参与者的平均（SE）总海马体积低于白色参与者（6418.26 [138.97] vs 6990.50 [44.10] mm（3））。非裔美国人受试者中总tau蛋白的平均（SE）CSF浓度低于白色受试者（293.65 [34.61] vs 443.28 [18.20] pg/mL; P < .001），磷酸化tau 181的平均（SE）浓度也是如此（53.18 [4.91] vs 70.73 [2.46] pg/mL; P < .001）。有一个显着的种族载脂蛋白E β 4相互作用的CSF总tau蛋白和磷酸化的tau 181，只有载脂蛋白E β 4阳性的参与者表现出种族差异。结论和相关性-本研究的结果表明，阿尔茨海默病的分子生物标志物的分析应调整种族。非裔美国人中总tau和磷酸化tau 181的较低CSF浓度似乎反映了APOE ε 4相互作用的显着种族，表明与白色个体相比，这种阿尔茨海默病风险变体在非裔美国人中的影响不同。
IMPORTANCE Racial differences in molecular biomarkers for Alzheimer disease may suggest race-dependent biological mechanisms.OBJECTIVE To ascertain whether there are racial disparities in molecular biomarkers for Alzheimer disease.DESIGN, SETTING, AND PARTICIPANTS A total of 1255 participants (173 African Americans) were enrolled from January 1, 2004, through December 31, 2015, in longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University and completed a magnetic resonance imaging study of the brain and/or positron emission tomography of the brain with Pittsburgh compound B (radioligand for aggregated amyloid-beta) and/or cerebrospinal fluid (CSF) assays for the concentrations of amyloid-beta 42, total tau, and phosphorylated tau181. Independent cross-sectional analyses were conducted from April 22, 2016, to August 27, 2018, for each biomarker modality with an analysis of variance or analysis of covariance including age, sex, educational level, race, apolipoprotein E (APOE) epsilon 4 allele status, and clinical status (normal cognition or dementia). All biomarker assessments were conducted without knowledge of the clinical status of the participants.MAIN OUTCOMES AND MEASURES The primary outcomes were hippocampal volumes adjusted for differences in intracranial volumes, global cerebral amyloid burden as transformed into standardized uptake value ratios (partial volume corrected), and CSF concentrations of amyloid-beta 42, total tau, and phosphorylated tau181.RESULTS Of the 1255 participants (707 women and 548 men; mean [SD] age, 70.8 [9.9] years), 116 of 173 African American participants (67.1%) and 724 of 1082 non-Hispanic white participants (66.9%) had normal cognition. There were no racial differences in the frequency of cerebral ischemic lesions noted on results of brain magnetic resonance imaging, mean cortical standardized uptake value ratios for Pittsburgh compound B, or for amyloid-beta 42 concentrations in CSF. However, in individuals with a reported family history of dementia, mean (SE) total hippocampal volumes were lower for African American participants than for white participants (6418.26 [138.97] vs 6990.50 [44.10] mm(3)). Mean (SE) CSF concentrations of total tau were lower in African American participants than in white participants (293.65 [34.61] vs 443.28 [18.20] pg/mL; P < .001), as were mean (SE) concentrations of phosphorylated tau181 (53.18 [4.91] vs 70.73 [2.46] pg/mL; P < .001). There was a significant race by APOE epsilon 4 interaction for both CSF total tau and phosphorylated tau181 such that only APOE epsilon 4-positive participants showed the racial differences.CONCLUSIONS AND RELEVANCE The results of this study suggest that analyses of molecular biomarkers of Alzheimer disease should adjust for race. The lower CSF concentrations of total tau and phosphorylated tau181 in African American individuals appear to reflect a significant race by APOE epsilon 4 interaction, suggesting a differential effect of this Alzheimer risk variant in African American individuals compared with white individuals.