用于预测刚果民主共和国金沙萨疑似阿尔茨海默病老年人海马萎缩的神经退行性血浆生物标志物

Neurodegenerative Plasma Biomarkers for Prediction of Hippocampal Atrophy in Older Adults with Suspected Alzheimer's Disease in Kinshasa, Democratic Republic of Congo.

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, Lago Argentina Lario, Kramer Joel H, Boxer Adam L, Jeromin Andreas, Hanseeuw Bernard, Gross Alden L, Alonso Alvaro

机构信息

Emory University School of Medicine, Department of Rehabilitation Medicine, Atlanta, GA 30322, USA.

University of Kinshasa and Catholic University of Congo, School of Medicine, Kinshasa, Department of Psychiatry, B.P. 7463 Kinshasa I, Democratic Republic of Congo.

出版信息

medRxiv. 2024 Sep 4:2024.09.03.24313019. doi: 10.1101/2024.09.03.24313019.

DOI:10.1101/2024.09.03.24313019

PMID:39281728

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398445/

Abstract

OBJECTIVE

The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias-amyloid-β (Aβ42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)-to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC).

METHODS

Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer's Questionnaire (AQ). Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood samples collected at the study visit. Hippocampal volumes were measured using magnetic resonance imaging (MRI). General linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under the curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either individually or in combination in the models.

RESULTS

Elevated p-tau181 was associated with left hippocampal (LH) atrophy p= 0.020). Only higher p-tau181 concentrations were significantly associated with 4.2-fold increased odds [OR=4.2 (1.5-18.4)] of hippocampal atrophy per standard deviation. The AUC of plasma biomarkers without clinical covariates to discriminate LH, RH, and total hippocampal (TH) or both hippocampi atrophy ranged between 90% to 94%, 76% to 82%, and 85% to 87%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, and TH ranged between 94%-96%, 81%-84%, and 88%-90%, respectively.

CONCLUSION

These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa.

摘要

目的

海马体是受阿尔茨海默病（AD）影响的首批脑结构之一，其萎缩是该疾病的一个重要指标。本研究调查了AD及AD相关痴呆症的血浆生物标志物——淀粉样β蛋白（Aβ42/40）、磷酸化tau蛋白181（p-tau181）、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）——预测刚果民主共和国金沙萨成年个体海马体萎缩的能力。

方法

使用痴呆症社区筛查工具和阿尔茨海默病问卷（AQ）对85名65岁以上的成年人（40名健康者和45名疑似AD患者）进行评估。在研究访视时采集的血样中测量核心AD生物标志物（Aβ42/40和p-tau181）以及非特异性神经退行性变生物标志物（NfL、GFAP）。使用磁共振成像（MRI）测量海马体体积。采用一般线性回归评估神经状态下生物标志物浓度的差异。使用逻辑回归模型绘制受试者工作特征曲线，并计算有无临床协变量时的曲线下面积（AUC），以确定生物标志物浓度预测海马体萎缩的能力。在模型中单独或联合使用血浆生物标志物。

结果

p-tau181升高与左侧海马体（LH）萎缩相关（p = 0.020）。每标准差下，只有较高的p-tau181浓度与海马体萎缩几率增加4.2倍[比值比（OR）=4.2（1.5 - 18.4）]显著相关。无临床协变量时，血浆生物标志物区分LH、右侧海马体（RH）和总海马体（TH）或双侧海马体萎缩的AUC分别在90%至94%、76%至82%和85%至87%之间。联合使用临床协变量和AD生物标志物的模型区分LH、RH和TH的AUC分别在94% - 96%、81% - 84%和88% - 90%之间。