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

doi:10.1038/s43856-024-00690-w

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 GlanzEnise 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	262
Journal	Communications Medicine
Volume	4
Issue number	1
Early online date	10 Dec 2024
DOIs	https://doi.org/10.1038/s43856-024-00690-w
Publication status	E-pub ahead of print - 10 Dec 2024

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s43856-024-00690-wFinal published version, 2.35 MBLicence: Creative Commons: Attribution (CC-BY)

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Blömeke, L., Rehn, F., Pils, M., Kraemer-Schulien, V., Cousin, A., Kutzsche, J., Bujnicki, T., Freiesleben, S. D., Schneider, L.-S., Preis, L., Priller, J., Spruth, E. J., Altenstein, S., Schneider, A., Fliessbach, K., Wiltfang, J., Hansen, N., Rostamzadeh, A., Düzel, E., ... Willbold, D. (2024). Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects. Communications Medicine, 4(1), 262. Advance online publication. https://doi.org/10.1038/s43856-024-00690-w

@article{55d55136fc694842b12a6f41a5b5c129,

title = "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 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.",

author = "Lara Bl{\"o}meke and Fabian Rehn and Marlene Pils and Victoria Kraemer-Schulien and Anneliese Cousin and Janine Kutzsche and Tuyen Bujnicki and Freiesleben, {Silka D} and Luisa-Sophie Schneider and Lukas Preis and Josef Priller and Spruth, {Eike J} and Slawek Altenstein and Anja Schneider and Klaus Fliessbach and Jens Wiltfang and Niels Hansen and Ayda Rostamzadeh and Emrah D{\"u}zel and Wenzel Glanz and Incesoy, {Enise I} and Katharina Buerger and Daniel Janowitz and Michael Ewers and Robert Perneczky and Boris-Stephan Rauchmann and Stefan Teipel and Ingo Kilimann and Christoph Laske and Munk, {Matthias H} and Annika Spottke and Nina Roy and Heneka, {Michael T} and Frederic Brosseron and Michael Wagner and Sandra Roeske and Alfredo Ramirez and Matthias Schmid and Frank Jessen and Oliver Bannach and Oliver Peters and Dieter Willbold",

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Blömeke, L, Rehn, F, Pils, M, Kraemer-Schulien, V, Cousin, A, Kutzsche, J, Bujnicki, T, Freiesleben, SD, Schneider, L-S, Preis, L, Priller, J, Spruth, EJ, Altenstein, S, Schneider, A, Fliessbach, K, Wiltfang, J, Hansen, N, Rostamzadeh, A, Düzel, E, Glanz, W, Incesoy, EI, Buerger, K, Janowitz, D, Ewers, M, Perneczky, R, Rauchmann, B-S, Teipel, S, Kilimann, I, Laske, C, Munk, MH, Spottke, A, Roy, N, Heneka, MT, Brosseron, F, Wagner, M, Roeske, S, Ramirez, A, Schmid, M, Jessen, F, Bannach, O, Peters, O & Willbold, D 2024, 'Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects', Communications Medicine, vol. 4, no. 1, pp. 262. https://doi.org/10.1038/s43856-024-00690-w

TY - JOUR

T1 - Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects

AU - Blömeke, Lara

AU - Rehn, Fabian

AU - Pils, Marlene

AU - Kraemer-Schulien, Victoria

AU - Cousin, Anneliese

AU - Kutzsche, Janine

AU - Bujnicki, Tuyen

AU - Freiesleben, Silka D

AU - Schneider, Luisa-Sophie

AU - Preis, Lukas

AU - Priller, Josef

AU - Spruth, Eike J

AU - Altenstein, Slawek

AU - Schneider, Anja

AU - Fliessbach, Klaus

AU - Wiltfang, Jens

AU - Hansen, Niels

AU - Rostamzadeh, Ayda

AU - Düzel, Emrah

AU - Glanz, Wenzel

AU - Incesoy, Enise I

AU - Buerger, Katharina

AU - Janowitz, Daniel

AU - Ewers, Michael

AU - Perneczky, Robert

AU - Rauchmann, Boris-Stephan

AU - Teipel, Stefan

AU - Kilimann, Ingo

AU - Laske, Christoph

AU - Munk, Matthias H

AU - Spottke, Annika

AU - Roy, Nina

AU - Heneka, Michael T

AU - Brosseron, Frederic

AU - Wagner, Michael

AU - Roeske, Sandra

AU - Ramirez, Alfredo

AU - Schmid, Matthias

AU - Jessen, Frank

AU - Bannach, Oliver

AU - Peters, Oliver

AU - Willbold, Dieter

PY - 2024/12/10

Y1 - 2024/12/10

N2 - 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.

AB - 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.

U2 - 10.1038/s43856-024-00690-w

DO - 10.1038/s43856-024-00690-w

M3 - Article

C2 - 39658587

SN - 2730-664X

VL - 4

SP - 262

JO - Communications Medicine

JF - Communications Medicine

IS - 1

ER -

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects

Abstract

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