Department of Neurology, Emory University School of Medicine, 615 Michael Street, 505F, Atlanta, GA, 30322, USA.
Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA, USA.
Alzheimers Res Ther. 2017 Nov 2;9(1):88. doi: 10.1186/s13195-017-0315-1.
African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.
We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).
Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p = 0.001) and p-tau/Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.
Despite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.
ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.
据报道，非裔美国人患阿尔茨海默病（AD）的比例高于白种人，但尚未对年龄较大的非裔美国人群体进行病因特异性 AD 生物标志物的系统分析。同时并存的脑血管病也可能导致这种发病率的增加。我们假设，在认知正常和与 AD 相关的认知障碍的年龄较大的非裔美国人和白种人中，脑脊液（CSF）淀粉样蛋白、神经退行性变和内皮功能障碍的生物标志物将有所不同。
我们前瞻性地招募了 135 名年龄较大的美国人，于 2013 年至 2015 年在佐治亚州亚特兰大市的埃默里大学接受详细的临床、神经心理学、遗传、磁共振成像（MRI）和 CSF 分析。我们比较了 CSF 标志物β-淀粉样蛋白（Aβ42、Aβ40）、总 tau 和磷酸化 tau（分别为 t-tau 和 p-tau）、内皮功能障碍（可溶性血管细胞黏附分子 1、可溶性细胞间黏附分子 1）、α-突触核蛋白和神经退行性变（神经丝轻链 [NfL]），以及 MRI 标志物，包括海马萎缩和脑血管病（白质高信号 [WMH] 体积）。
共纳入 65 名年龄较大的非裔美国人（平均年龄 69.1 岁）和 70 名年龄较大的白种人（平均年龄 70.8 岁）。在调整了人口统计学变量、AD 风险等位基因和认知功能后，尽管 Aβ42 水平相似，非裔美国人的 p-tau（差异 7.4pg/ml；95%CI，3.7-11.2pg/ml；p<0.001）、t-tau（差异 23.6pg/ml；95%CI，9.5-37.7；p=0.001）和 Aβ40（差异 1.35ng/ml；95%CI，0.29-2.42ng/ml；p=0.013）水平较低。认知障碍的非裔美国人的 t-tau/Aβ42（复合认知每 1-SD 变化的差异为 0.255；95%CI，0.100-0.409；p=0.001）和 p-tau/Aβ42（复合认知每 1-SD 变化的差异为 0.076；95%CI，0.031-0.122；p=0.001）也较低。这不能用非 AD 过程的测量生物标志物来解释，但非裔美国人可能比白种人更容易受到 WMH 的认知影响。
尽管 CSF Aβ42 和 Aβ42/Aβ40 水平相似，但非裔美国人的认知障碍与 CSF tau 标志物的变化较小有关，但与白种人相比，WMH 负担的影响更大。CSF tau 标志物和比值的种族相关差异可能导致非裔美国人 AD 的诊断不足。
ClinicalTrials.gov，NCT02089555。2014 年 3 月 14 日回顾性注册。
