基于血液的Aβ寡聚体定量分析表明，ApoE ε4阳性受试者的大脑清除功能受损。
Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.
作者信息
Blömeke Lara, Rehn Fabian, Pils Marlene, Kraemer-Schulien Victoria, Cousin Anneliese, Kutzsche Janine, Bujnicki Tuyen, Freiesleben Silka D, Schneider Luisa-Sophie, Preis Lukas, Priller Josef, Spruth Eike J, Altenstein Slawek, Schneider Anja, Fliessbach Klaus, Wiltfang Jens, Hansen Niels, Rostamzadeh Ayda, Düzel Emrah, Glanz Wenzel, Incesoy Enise I, Buerger Katharina, Janowitz Daniel, Ewers Michael, Perneczky Robert, Rauchmann Boris-Stephan, Teipel Stefan, Kilimann Ingo, Laske Christoph, Munk Matthias H, Spottke Annika, Roy Nina, Heneka Michael T, Brosseron Frederic, Wagner Michael, Roeske Sandra, Ramirez Alfredo, Schmid Matthias, Jessen Frank, Bannach Oliver, Peters Oliver, Willbold Dieter
机构信息
Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
attyloid GmbH, 40225, Düsseldorf, Germany.
出版信息
Commun Med (Lond). 2024 Dec 10;4(1):262. doi: 10.1038/s43856-024-00690-w.
BACKGROUND
Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.
METHODS
In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.
RESULTS
The blood-based sFIDA assay delivers a sensitivity of 1.8 fM, an inter- and intra-assay variation below 20% for oligomer calibration standards and no interference with matrix components. Quantification of Aβ oligomers in 359 plasma samples from the DELCODE cohort reveals lower oligomer concentrations in subjective cognitive decline and AD patients than healthy Control participants.
CONCLUSIONS
Correlation analysis between CSF and plasma oligomer concentrations indicates an impaired clearance of Aβ oligomers that is dependent on the ApoE ε4 status.
背景
血浆中β淀粉样蛋白（Aβ）寡聚体的定量分析有助于阿尔茨海默病（AD）的早期诊断，并增进我们对潜在病理机制的理解。然而，由于Aβ寡聚体浓度极低且可能受到基质成分的干扰，定量分析需要一种极其灵敏且具选择性的技术。
方法
在本报告中，我们开发并验证了一种基于表面的荧光分布分析（sFIDA）测定法，用于定量分析血浆中的Aβ寡聚体。
结果
基于血液的sFIDA测定法灵敏度为1.8 fM，寡聚体校准标准品的批间和批内变异低于20%，且不受基质成分干扰。对DELCODE队列中359份血浆样本的Aβ寡聚体进行定量分析发现，主观认知功能下降和AD患者的寡聚体浓度低于健康对照参与者。
结论
脑脊液和血浆寡聚体浓度之间的相关性分析表明，Aβ寡聚体清除受损，且这种清除受损取决于载脂蛋白Eε4状态。
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