Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects
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 oligom...
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Nature Portfolio
2024-12-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00690-w |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lara Blömeke |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-591b1f2f6da445b29a6021effbebac6c |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-591b1f2f6da445b29a6021effbebac6c2024-12-15T12:12:20ZengNature PortfolioCommunications Medicine2730-664X2024-12-014111310.1038/s43856-024-00690-wBlood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjectsLara Blömeke0Fabian Rehn1Marlene Pils2Victoria Kraemer-Schulien3Anneliese Cousin4Janine Kutzsche5Tuyen Bujnicki6Silka D. Freiesleben7Luisa-Sophie Schneider8Lukas Preis9Josef Priller10Eike J. Spruth11Slawek Altenstein12Anja Schneider13Klaus Fliessbach14Jens Wiltfang15Niels Hansen16Ayda Rostamzadeh17Emrah Düzel18Wenzel Glanz19Enise I. Incesoy20Katharina Buerger21Daniel Janowitz22Michael Ewers23Robert Perneczky24Boris-Stephan Rauchmann25Stefan Teipel26Ingo Kilimann27Christoph Laske28Matthias H. Munk29Annika Spottke30Nina Roy31Michael T. Heneka32Frederic Brosseron33Michael Wagner34Sandra Roeske35Alfredo Ramirez36Matthias Schmid37Frank Jessen38Oliver Bannach39Oliver Peters40Dieter Willbold41Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of GoettingenDepartment of Psychiatry, University of Cologne, Medical FacultyGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE, Munich)Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichGerman Center for Neurodegenerative Diseases (DZNE, Munich)German Center for Neurodegenerative Diseases (DZNE, Munich)Department of Psychiatry and Psychotherapy, University Hospital, LMU MunichGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichGerman Center for Neurodegenerative Diseases (DZNE)Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichAbstract 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.https://doi.org/10.1038/s43856-024-00690-w |
| spellingShingle | 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 Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects Communications Medicine |
| title | Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects |
| title_full | Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects |
| title_fullStr | Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects |
| title_full_unstemmed | Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects |
| title_short | Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects |
| title_sort | blood based quantification of aβ oligomers indicates impaired clearance from brain in apoe ε4 positive subjects |
| url | https://doi.org/10.1038/s43856-024-00690-w |
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