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Blömeke, Lara ORCID logoORCID: https://orcid.org/0000-0002-8861-9224; Rehn, Fabian ORCID logoORCID: https://orcid.org/0000-0001-8815-0684; Pils, Marlene ORCID logoORCID: https://orcid.org/0000-0002-1506-3675; Kraemer-Schulien, Victoria ORCID logoORCID: https://orcid.org/0000-0002-7413-7646; Cousin, Anneliese; Kutzsche, Janine ORCID logoORCID: https://orcid.org/0000-0003-0271-7390; Bujnicki, Tuyen ORCID logoORCID: https://orcid.org/0000-0002-7191-8455; Freiesleben, Silka D. ORCID logoORCID: https://orcid.org/0000-0002-2141-8671; Schneider, Luisa-Sophie ORCID logoORCID: https://orcid.org/0000-0001-5822-1744; Preis, Lukas; Priller, Josef; Spruth, Eike J.; Altenstein, Slawek; Schneider, Anja ORCID logoORCID: https://orcid.org/0000-0001-9540-8700; Fliessbach, Klaus; Wiltfang, Jens ORCID logoORCID: https://orcid.org/0000-0003-1492-5330; Hansen, Niels ORCID logoORCID: https://orcid.org/0000-0001-5785-9594; Rostamzadeh, Ayda; Düzel, Emrah; Glanz, Wenzel; Incesoy, Enise I. ORCID logoORCID: https://orcid.org/0000-0003-2014-4098; Buerger, Katharina ORCID logoORCID: https://orcid.org/0000-0002-5898-9953; Janowitz, Daniel ORCID logoORCID: https://orcid.org/0009-0003-4090-547X; Ewers, Michael; Perneczky, Robert ORCID logoORCID: https://orcid.org/0000-0003-1981-7435; Rauchmann, Boris-Stephan ORCID logoORCID: https://orcid.org/0000-0003-4547-6240; Teipel, Stefan; Kilimann, Ingo; Laske, Christoph; Munk, Matthias H.; Spottke, Annika; Roy, Nina; Heneka, Michael T. ORCID logoORCID: https://orcid.org/0000-0003-4996-1630; Brosseron, Frederic ORCID logoORCID: https://orcid.org/0000-0003-3137-7516; Wagner, Michael ORCID logoORCID: https://orcid.org/0000-0003-2589-6440; Roeske, Sandra; Ramirez, Alfredo ORCID logoORCID: https://orcid.org/0000-0003-4991-763X; Schmid, Matthias; Jessen, Frank; Bannach, Oliver; Peters, Oliver und Willbold, Dieter ORCID logoORCID: https://orcid.org/0000-0002-0065-7366 (2024): Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects. In: Communications Medicine, Bd. 4, 262 [PDF, 2MB]

Abstract

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.

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