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刚果有或无痴呆症个体中阿尔茨海默病血浆生物标志物的初步参考值。

Preliminary reference values for Alzheimer's disease plasma biomarkers in Congolese individuals with and without dementia.

作者信息

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

机构信息

Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, GA, United States.

Department of Psychiatry, School of Medicine, University of Kinshasa and Catholic University of Congo, Kinshasa, Democratic Republic of Congo.

出版信息

Front Aging Neurosci. 2024 Nov 21;16:1477047. doi: 10.3389/fnagi.2024.1477047. eCollection 2024.

Abstract

BACKGROUND

Western countries have provided reference values (RV) for Alzheimer's 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- (Aβ42/40), 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 (TNFα) 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 Aβ42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα 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 Youden's index.

RESULTS

In this sample of 85 adults, 45 (53%) had dementia, 38 (45%) 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 normal value cutoffs of various plasma in pg./mL were 0.061 for Aβ42/40, 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 [0.72 (95% CI: 0.59, 0.84)] followed by GFAP [0.72 (95% CI: 0.61, 0.83)], and Nfl [0.73 (95% CI: 0.62, 0.84)] had the highest AUC compared to other plasma biomarkers.

CONCLUSION

This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, and classification, of dementia in Congolese adults.

摘要

背景

西方国家已提供阿尔茨海默病(AD)血浆生物标志物的参考值(RV),但撒哈拉以南非洲人群尚无此类参考值。

目的

我们为患有和未患痴呆症的刚果成年人提供AD及其他血浆生物标志物的初步参考值,这些生物标志物包括淀粉样蛋白(Aβ42/40)、磷酸化tau-181和217(p-tau181、p-tau217)、神经丝轻链(Nfl)、胶质纤维酸性蛋白(GFAP)、白细胞介素1β和10(IL-1β和IL-10)以及肿瘤坏死因子α(TNFα)。

方法

纳入85名50岁以上的成年人(40名健康者和45名痴呆患者)。采集血样用于检测血浆AD生物标志物Aβ42/40和p-tau181、p-tau217;Nfl和GFAP;IL-1β和IL-10以及TNFα,采用单分子阵列免疫检测技术(SIMOA)进行分析。进行线性和逻辑回归以评估生物标志物在年龄、性别和神经状态方面的差异,以及每个个体生物标志物对痴呆状态的预测能力。参考值是基于约登指数优化敏感性和特异性的数值。

结果

在这85名成年人样本中,45名(53%)患有痴呆症,38名(45%)为男性,总体平均年龄为73.2(标准差7.6)岁,受教育年限为8.3(5.4)年。基于神经状态,年龄、性别和教育程度无显著差异。除p-tau181和GFAP外,生物标志物浓度在年龄方面无显著差异,在性别方面也无差异。各种血浆生物标志物的初步正常价值截断值(单位:pg./mL)分别为:Aβ42/40为0.061、p-tau 181为4.50、p-tau 217为0.008、Nfl为36.5、GFAP为176、TNFα为1.16、IL-1β为0.011、IL-10为0.38。所有曲线下面积(AUC)在0.64 - 0.74之间。与其他血浆生物标志物相比,p-tau 217[0.72(95%置信区间:0.59,0.84)]、其次是GFAP[0.72(95%置信区间:0.61,0.83)]和Nfl[0.73(95%置信区间:0.62,0.84)]的AUC最高。

结论

本研究提供的参考值可能有助于刚果成年人痴呆症的筛查、临床诊断判定和分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d92/11618107/997a3068df62/fnagi-16-1477047-g001.jpg

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