Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alzheimers Dement. 2023 Apr;19(4):1403-1414. doi: 10.1002/alz.12787. Epub 2022 Sep 24.
Plasma biomarkers will likely revolutionize the diagnostic work-up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect the levels of these biomarkers, and their clinical utility.
Participants with plasma and CSF biomarkers, creatinine, body mass index (BMI), and medical history data were included (BioFINDER-1: n = 748, BioFINDER-2: n = 421). We measured beta-amyloid (Aβ42, Aβ40), phosphorylated tau (p-tau217, p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).
In both cohorts, creatinine and BMI were the main factors associated with NfL, GFAP, and to a lesser extent with p-tau. However, adjustment for BMI and creatinine had only minor effects in models predicting either the corresponding levels in CSF or subsequent development of dementia.
Creatinine and BMI are related to certain plasma biomarkers levels, but they do not have clinically relevant confounding effects for the vast majority of individuals.
Creatinine and body mass index (BMI) are related to certain plasma biomarker levels. Adjusting for creatinine and BMI has minor influence on plasma-cerebrospinal fluid (CSF) associations. Adjusting for creatinine and BMI has minor influence on prediction of dementia using plasma biomarkers.
血浆生物标志物可能会在全球范围内彻底改变阿尔茨海默病（AD）的诊断方法。在广泛使用之前，我们需要确定是否有混杂因素会影响这些生物标志物的水平及其临床效用。
纳入了具有血浆和 CSF 生物标志物、肌酐、体重指数（BMI）和病史数据的参与者（BioFINDER-1：n=748，BioFINDER-2：n=421）。我们测量了β-淀粉样蛋白（Aβ42、Aβ40）、磷酸化 tau（p-tau217、p-tau181）、神经丝轻链（NfL）和神经胶质纤维酸性蛋白（GFAP）。
在两个队列中，肌酐和 BMI 是与 NfL、GFAP 相关的主要因素，与 p-tau 的相关性较小。然而，在预测 CSF 中相应水平或随后发生痴呆的模型中，调整 BMI 和肌酐仅对少数个体具有较小的影响。
肌酐和 BMI 与某些血浆生物标志物水平相关，但对大多数个体来说，它们没有临床相关的混杂影响。
肌酐和体重指数（BMI）与某些血浆生物标志物水平相关。肌酐和 BMI 的调整对血浆-脑脊液（CSF）关联的影响较小。肌酐和 BMI 的调整对使用血浆生物标志物预测痴呆的影响较小。
