Communications Medicine (Dec 2024)
Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects
- Lara Blömeke,
- Fabian Rehn,
- Marlene Pils,
- Victoria Kraemer-Schulien,
- Anneliese Cousin,
- Janine Kutzsche,
- Tuyen Bujnicki,
- Silka D. Freiesleben,
- Luisa-Sophie Schneider,
- Lukas Preis,
- Josef Priller,
- Eike J. Spruth,
- Slawek Altenstein,
- Anja Schneider,
- Klaus Fliessbach,
- Jens Wiltfang,
- Niels Hansen,
- Ayda Rostamzadeh,
- Emrah Düzel,
- Wenzel Glanz,
- Enise I. Incesoy,
- Katharina Buerger,
- Daniel Janowitz,
- Michael Ewers,
- Robert Perneczky,
- Boris-Stephan Rauchmann,
- Stefan Teipel,
- Ingo Kilimann,
- Christoph Laske,
- Matthias H. Munk,
- Annika Spottke,
- Nina Roy,
- Michael T. Heneka,
- Frederic Brosseron,
- Michael Wagner,
- Sandra Roeske,
- Alfredo Ramirez,
- Matthias Schmid,
- Frank Jessen,
- Oliver Bannach,
- Oliver Peters,
- Dieter Willbold
Affiliations
- Lara Blömeke
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Fabian Rehn
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Marlene Pils
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Victoria Kraemer-Schulien
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Anneliese Cousin
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Janine Kutzsche
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Tuyen Bujnicki
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Silka D. Freiesleben
- German Center for Neurodegenerative Diseases (DZNE)
- Luisa-Sophie Schneider
- German Center for Neurodegenerative Diseases (DZNE)
- Lukas Preis
- German Center for Neurodegenerative Diseases (DZNE)
- Josef Priller
- German Center for Neurodegenerative Diseases (DZNE)
- Eike J. Spruth
- German Center for Neurodegenerative Diseases (DZNE)
- Slawek Altenstein
- German Center for Neurodegenerative Diseases (DZNE)
- Anja Schneider
- German Center for Neurodegenerative Diseases (DZNE)
- Klaus Fliessbach
- German Center for Neurodegenerative Diseases (DZNE)
- Jens Wiltfang
- German Center for Neurodegenerative Diseases (DZNE)
- Niels Hansen
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen
- Ayda Rostamzadeh
- Department of Psychiatry, University of Cologne, Medical Faculty
- Emrah Düzel
- German Center for Neurodegenerative Diseases (DZNE)
- Wenzel Glanz
- German Center for Neurodegenerative Diseases (DZNE)
- Enise I. Incesoy
- German Center for Neurodegenerative Diseases (DZNE)
- Katharina Buerger
- German Center for Neurodegenerative Diseases (DZNE, Munich)
- Daniel Janowitz
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich
- Michael Ewers
- German Center for Neurodegenerative Diseases (DZNE, Munich)
- Robert Perneczky
- German Center for Neurodegenerative Diseases (DZNE, Munich)
- Boris-Stephan Rauchmann
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich
- Stefan Teipel
- German Center for Neurodegenerative Diseases (DZNE)
- Ingo Kilimann
- German Center for Neurodegenerative Diseases (DZNE)
- Christoph Laske
- German Center for Neurodegenerative Diseases (DZNE)
- Matthias H. Munk
- German Center for Neurodegenerative Diseases (DZNE)
- Annika Spottke
- German Center for Neurodegenerative Diseases (DZNE)
- Nina Roy
- German Center for Neurodegenerative Diseases (DZNE)
- Michael T. Heneka
- Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg
- Frederic Brosseron
- German Center for Neurodegenerative Diseases (DZNE)
- Michael Wagner
- German Center for Neurodegenerative Diseases (DZNE)
- Sandra Roeske
- German Center for Neurodegenerative Diseases (DZNE)
- Alfredo Ramirez
- German Center for Neurodegenerative Diseases (DZNE)
- Matthias Schmid
- German Center for Neurodegenerative Diseases (DZNE)
- Frank Jessen
- German Center for Neurodegenerative Diseases (DZNE)
- Oliver Bannach
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- Oliver Peters
- German Center for Neurodegenerative Diseases (DZNE)
- Dieter Willbold
- Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich
- DOI
- https://doi.org/10.1038/s43856-024-00690-w
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 13
Abstract
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.