Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Alzheimers Dement. 2024 Feb;20(2):1284-1297. doi: 10.1002/alz.13518. Epub 2023 Nov 20.
Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.
We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CV ) and between-subject (CV ) BV, analytical variation, and reference change values (RCV).
Biomarkers presented considerable variability in CV and CV . Aβ42/Aβ40 had the lowest CV (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).
BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
血液生物标志物已被证明在阿尔茨海默病（AD）研究中有用。然而，关于它们的生物学变异（BV）知之甚少，这可以提高个体水平数据的解释能力。
我们在欧洲生物变异研究中，从 20 名年龄在 40 至 60 岁的参与者中每周采集一次血浆样本，共采集 10 周，测量了血浆中的淀粉样蛋白β（Aβ42、Aβ40）、磷酸化 tau（p-tau181、p-tau217、p-tau231）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）。我们估计了个体内（CV ）和个体间（CV ）BV、分析变异和参考变化值（RCV）。
生物标志物的 CV 和 CV 差异较大。Aβ42/Aβ40 的 CV 最低（≈3%），p-tau181 的 CV 最高（≈16%），而其他生物标志物的 CV 范围在 6%至 10%之间。大多数 RCV 范围在 20%至 30%（下降）和 25%至 40%（上升）之间。
AD 血浆生物标志物的 BV 估计值可能会改进其临床和研究解释。当监测早期疾病进展或干预时，RCV 可能有助于检测连续测量值之间的显著变化。
血浆淀粉样蛋白β（Aβ42/Aβ40）在个体内和个体间的生物学变异最小，但在 AD 患者与对照组相比变化最小。血浆磷酸化 tau 变体在个体内的生物学变异差异显著，但在 AD 中的显著变化可能限制了其变异性的影响。血浆神经丝轻链和神经胶质纤维酸性蛋白表现出高个体间变异，其影响将取决于临床背景。RCV 可能有助于在个体水平上监测早期疾病进展和干预的安全性/疗效。连续采样显示，在健康个体中可能会观察到出乎意料的高值，这在基于单次测试结果解释 AD 血浆生物标志物时需要谨慎。
Zotero 插件
