Vincent Malotaux, Nicholas J. Ashton, Annika Öhrfelt, Yinghua Chen, Yi Su, Gloria Garcia-Ospina, Claudia Guzman-Martínez, Andres Villegas-Lanau, Johana Gómez-Ramirez, Margarita Giraldo-Chica, David Aguillon, Victoria Tirado, Ana Baena, Claudia Munoz, Natalia Acosta-Baena, Jeremy J. Pruzin, Valentina Ghisays, Silvia Rios-Romenets, Clara Vila-Castelar, Jairo E. Martínez, Averi Giudicessi, Pierre N. Tariot, Henrik Zetterberg, Kaj Blennow, Eric M. Reiman, Yakeel T. Quiroz
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We evaluated its diagnostic value in presenilin 1 (<i>PSEN1</i>) E280A mutation carriers versus non-carriers and compared it to p-tau217 and neurofilament light chain (NfL).</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We analyzed plasma p-tau231 in 722 carriers and 640 non-carriers (ages 18–75). Longitudinal data from 164 carriers and 132 non-carriers were available, with 137 carriers and 109 non-carriers having p-tau231, p-tau217, and NfL levels. Analyses used linear mixed effects models and restricted cubic splines.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>E280A carriers had higher p-tau231 levels than non-carriers (9.0 ± 7.4 vs. 5.2 ± 3.4 pg/mL, <i>P</i> < 0.001). Baseline p-tau231 levels correlated with age, distinguishing carriers at age 23. Rates of change differed at age 19, ≈ 25 years before cognitive impairment. 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引用次数: 0
摘要
血浆磷酸化tau (p-tau)-231是一种很有前景的阿尔茨海默病（AD）生物标志物，特别是在临床前阶段。我们评估了其在早老素1 (PSEN1) E280A突变携带者与非携带者中的诊断价值，并将其与p-tau217和神经丝轻链（NfL）进行了比较。方法我们分析了722名携带者和640名非携带者（18-75岁）的血浆p-tau231。来自164名携带者和132名非携带者的纵向数据可用，其中137名携带者和109名非携带者具有p-tau231， p-tau217和NfL水平。分析使用线性混合效应模型和限制三次样条。结果E280A携带者P -tau231水平高于非携带者(9.0±7.4 vs 5.2±3.4 pg/mL, P <；0.001)。基线p-tau231水平与年龄相关，在23岁时区分携带者。在认知障碍发生前约25年，即19岁时，其变化率不同。在一个子集中，p-tau231在20岁时改变了分化的携带者，比p-tau217和NfL早。血浆p-tau231是早期AD检测和进展监测的敏感生物标志物。血浆磷酸化tau (p-tau)231水平与早老素1携带者和非携带者的年龄相关。在23岁时，p-tau231的基线水平在携带者和非携带者之间存在差异。血浆p-tau231的变化在19岁时就能区分出携带者，这是非常早期的阶段。P-tau231的纵向变化早于p-tau217或神经丝轻链。
Plasma p-tau231 in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: A cross-sectional and longitudinal cohort study
INTRODUCTION
Plasma phosphorylated tau (p-tau)-231 is a promising biomarker for Alzheimer's disease (AD), particularly in preclinical stages. We evaluated its diagnostic value in presenilin 1 (PSEN1) E280A mutation carriers versus non-carriers and compared it to p-tau217 and neurofilament light chain (NfL).
METHODS
We analyzed plasma p-tau231 in 722 carriers and 640 non-carriers (ages 18–75). Longitudinal data from 164 carriers and 132 non-carriers were available, with 137 carriers and 109 non-carriers having p-tau231, p-tau217, and NfL levels. Analyses used linear mixed effects models and restricted cubic splines.
RESULTS
E280A carriers had higher p-tau231 levels than non-carriers (9.0 ± 7.4 vs. 5.2 ± 3.4 pg/mL, P < 0.001). Baseline p-tau231 levels correlated with age, distinguishing carriers at age 23. Rates of change differed at age 19, ≈ 25 years before cognitive impairment. In a subset, p-tau231 changes differentiated carriers by age 20, earlier than p-tau217 and NfL.
DISCUSSION
Plasma p-tau231 is a sensitive biomarker for early AD detection and progression monitoring.
Highlights
Plasma phosphorylated tau (p-tau)231 levels are associated with age in presenilin 1 carriers and non-carriers.
Baseline p-tau231 levels diverged between carriers and non-carriers at age 23.
Plasma p-tau231 changes distinguished carriers by age 19, at very early stages.
P-tau231 longitudinal changes differentiate carriers earlier than p-tau217 or neurofilament light chain.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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