Department of Neurology, Emory University School of Medicine, Emory Brain Health Center, Atlanta, GA, USA.
Emory Goizueta Alzheimer's Disease Research Center, Emory University, Atlanta, GA, USA.
Ann Neurol. 2024 Sep;96(3):463-475. doi: 10.1002/ana.26960. Epub 2024 Jun 25.
Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals.
We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions.
Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aβ was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%).
Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024;96:463-475.
据信,阿尔茨海默病(AD)在非裔美国人(AA)中更为常见,但针对 AA 人群的生物标志物研究有限。本报告代表了迄今为止对 AA 个体进行的最大规模的研究,旨在检查 AD 患者的脑脊液生物标志物。
我们使用阿尔茨海默病神经影像学倡议得出的截定点,并采用数据驱动的多元高斯混合回归分析了来自对照组、AD 病例和非 AD 病例的 3006 例脑脊液样本,其中包括 495 例(16.5%)自我认定的黑/AA 人群和 2456 例(81.7%)白/欧洲人。
在不同组别中发现了种族的不同影响。在所有组别中,AA 个体的总 Tau 和磷酸化 181-Tau 水平均较低(p<0.0001),且 AA 对照组的 Aβ 水平明显低于白对照组(p<0.0001)。通过纳入协变量调整的脑脊液分布高斯混合回归模型建模发现,AA 种族的系数估计值与年龄 20 年变化相当。使用阿尔茨海默病神经影像学倡议的截定点,AA 对照组中被归类为生物标志物阳性无症状 AD 的人数较少(8.0%比 13.4%)。在调整协变量后,我们的高斯混合回归模型缩小了这一差异,但仍然预测 AA 对照组中无症状 AD 的患病率较低(9.3%比 13.5%)。
尽管痴呆风险较高,但数据驱动的建模表明 AA 对照组中无症状 AD 的频率较低,这表明 AA 人群的痴呆症可能不是由更高的 AD 发病率驱动的。ANN NEUROL 2024;96:463-475。