Preliminary reference values for Alzheimers disease plasma biomarkers in Congolese individuals with and without Alzheimers disease

Jean Ikanga, Kharine Jean, Priscilla Medina, Saranya Sundaram Patel, Megan Claire Schwinne, Emmanuel Epenge, Guy Gikelekele, Nathan Tshengele, Immaculee Kavugho, Samuel Mampunza, Lelo Mananga, Charlotte Teunissen, Anthony Stringer, Julio Rojas, Brandon Chan, Argentina Lario Lago, Joel Kramer, Adam Boxer, Andreas Jeromin, Alden Gross, Alvaro Alonso
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Abstract

Background: Western countries have provided reference values (RV) for Alzheimers disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid-β (AB;42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor a; (TNFa) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers AB;42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFa; analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youdens index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for AB;42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.
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刚果阿尔茨海默氏症患者和非阿尔茨海默氏症患者血浆生物标志物的初步参考值
背景:西方国家提供了阿尔茨海默病(AD)血浆生物标志物的参考值(RV),但撒哈拉以南非洲地区的人群却没有。我们的目标是我们提供了患有和未患有痴呆症的刚果成年人的AD和其他血浆生物标记物的初步参考值,包括淀粉样蛋白-β(AB;42/40)、磷酸化tau-181和217(p-tau181和p-tau217)、神经丝光(Nfl)、胶质纤维酸性蛋白(GFAP)、白细胞介素1b和10(IL-1b和IL-10)以及肿瘤坏死因子a(TNFa)。方法:纳入 85 名 50 岁以上的成年人(40 名健康人和 45 名痴呆症患者)。提供血样,使用 SIMOA 分析血浆 AD 生物标记物 AB;42/40 和 p-tau181, p-tau217;Nfl 和 GFAP;IL-1b 和 IL-10 以及 TNFa。进行了线性回归和逻辑回归,以评估不同年龄、性别和神经系统状态下生物标志物的差异,并通过每个生物标志物预测痴呆状态。根据尤登斯指数优化灵敏度和特异性的生物标志物为 RV。结果在85名成人样本中,40人(47%)患有痴呆症,38人(45.0%)为男性,总平均年龄为73.2岁(标准差为7.6岁),受教育年限为8.3年(5.4年)。神经系统状况在年龄、性别和教育程度上没有明显差异。除 p-tau181 和 GFAP 外,生物标志物浓度在不同年龄段没有明显差异,在不同性别也没有差异。以 pg/ml 为单位的各种血浆初步临界值为:AB;42/40 为 0.061、p-tau 181 为 4.50、p-tau 217 为 0.008、Nfl 为 36.5、GFAP 为 176、TNFa 为 1.16、IL-1b 为 0.011、IL-10 为 0.38。所有 AUC 在 0.64-0.74 之间。与其他血浆生物标记物相比,P-tau 217 [0.74 (0.61, 0.86)]的AUC最高,其次是GFAP [0.72 (0.61, 0.83)]和Nfl [0.71 (0.60, 0.82)]。结论:本研究提供的 RV 可初步用于刚果成人注意力缺失症的筛查、临床诊断、分类和预后判断。
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