From the Department of Neurology and Neurological Sciences (K.D.D., V.N., M.D.G., E.C.M.), Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (R.A.S.), Brigham and Women's Hospital, Massachusetts General Hospital, Boston; Department of Neurology, The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, and The Institute for Genomic Medicine (R.M.), Columbia University Medical Center and The New York Presbyterian Hospital, New York; and Vanderbilt Memory and Alzheimer's Center and Vanderbilt Genetics Institute (T.H.), Nashville, TN.
Neurology. 2021 Mar 16;96(11):e1491-e1500. doi: 10.1212/WNL.0000000000011599. Epub 2021 Feb 10.
To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups.
We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of ε4 and ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with were assessed.
NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data.
Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.
研究在接受无症状阿尔茨海默病（A4）研究的淀粉样蛋白 PET 筛选的认知正常（CN）个体中，淀粉样蛋白 PET 是否因自我认定的非西班牙裔白人和黑人（NHW 和 NHB）群体而有所不同。
我们检查了 3689 名 NHW 和 144 名 NHB 参与者，他们通过了 A4 研究的初步筛选，并接受了淀粉样蛋白 PET 检查。使用逻辑（二分类组）和线性（连续值）回归，在控制年龄、性别和 ε4 和 ε2 等位基因数量的情况下，检查了种族对淀粉样蛋白 PET 的影响。在 NHB 组内测试了淀粉样蛋白与遗传确定的祖先（反映非洲、南亚、东亚、美洲和欧洲人群）之间的关联，并评估了与 ε4 的潜在相互作用。
与 NHW 参与者相比，NHB 参与者的淀粉样蛋白阳性率较低，连续淀粉样蛋白水平也较低。这种淀粉样蛋白种族效应在 ε4 组中最强。在 NHB 参与者中，具有较低非洲祖先百分比的个体具有较高的淀粉样蛋白。与 NHW 参与者相比，更多的 NHB 参与者未通过初始筛选，这表明 A4 PET 数据中与种族有关的潜在偏倚来源。
在通过 A4 研究初步入选标准的自我认定的 NHB 参与者中观察到减少的淀粉样蛋白。这项工作强调了在具有不同祖先的样本中研究 AD 生物标志物的重要性，以及在 AD 预防试验中仔细考虑研究入选标准的必要性。
