Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles

Coughlan, Christina; Lindenberger, Jared; Jacot, Jeffrey G.; Johnson, Noah R.; Anton, Paige; Bevers, Shaun; Welty, Robb; Graner, Michael W.; Potter, Huntington

doi:10.3390/ijms25073703

Open AccessArticle

Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles

by

Christina Coughlan

^1,*

,

Jared Lindenberger

^2,3,†,

Jeffrey G. Jacot

^4,†

,

Noah R. Johnson

¹,

Paige Anton

¹,

Shaun Bevers

²,

Robb Welty

²,

Michael W. Graner

⁵

and

Huntington Potter

¹

University of Colorado Alzheimer’s and Cognition Center (CUACC), Linda Crnic Institute for Down Syndrome (LCI), Department of Neurology, University of Colorado Anschutz Medical Campus, 13001 E. 17th Pl, Aurora, CO 80045, USA

²

Structural Biology and Biophysics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

³

Duke Human Vaccine Institute, Duke University, 2 Genome Ct., Durham, NC 27710, USA

⁴

Department of Bioengineering, University of Colorado Anschutz Medical Campus, 13001 E. 17th Pl, Aurora, CO 80045, USA

⁵

Department of Neurosurgery, University of Colorado Anschutz Medical Campus, 13001 E. 17th Pl, Aurora, CO 80045, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(7), 3703; https://doi.org/10.3390/ijms25073703

Submission received: 23 January 2024 / Revised: 14 March 2024 / Accepted: 19 March 2024 / Published: 26 March 2024

(This article belongs to the Section Molecular Biology)

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Abstract

Alzheimer’s disease (AD) is the fifth leading cause of death among adults aged 65 and older, yet the onset and progression of the disease is poorly understood. What is known is that the presence of amyloid, particularly polymerized Aβ42, defines when people are on the AD continuum. Interestingly, as AD progresses, less Aβ42 is detectable in the plasma, a phenomenon thought to result from Aβ becoming more aggregated in the brain and less Aβ42 and Aβ40 being transported from the brain to the plasma via the CSF. We propose that extracellular vesicles (EVs) play a role in this transport. EVs are found in bodily fluids such as blood, urine, and cerebrospinal fluid and carry diverse “cargos” of bioactive molecules (e.g., proteins, nucleic acids, lipids, metabolites) that dynamically reflect changes in the cells from which they are secreted. While Aβ42 and Aβ40 have been reported to be present in EVs, it is not known whether this interaction is specific for these peptides and thus whether amyloid-carrying EVs play a role in AD and/or serve as brain-specific biomarkers of the AD process. To determine if there is a specific interaction between Aβ and EVs, we used isothermal titration calorimetry (ITC) and discovered that Aβ42 and Aβ40 bind to EVs in a manner that is sequence specific, saturable, and endothermic. In addition, Aβ incubation with EVs overnight yielded larger amounts of bound Aβ peptide that was fibrillar in structure. These findings point to a specific amyloid–EV interaction, a potential role for EVs in the transport of amyloid from the brain to the blood, and a role for this amyloid pool in the AD process.

Keywords: extracellular vesicles (EVs); amyloid; isothermal titration calorimetry (ITC); atomic force microscopy (AFM)

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MDPI and ACS Style

Coughlan, C.; Lindenberger, J.; Jacot, J.G.; Johnson, N.R.; Anton, P.; Bevers, S.; Welty, R.; Graner, M.W.; Potter, H. Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles. Int. J. Mol. Sci. 2024, 25, 3703. https://doi.org/10.3390/ijms25073703

AMA Style

Coughlan C, Lindenberger J, Jacot JG, Johnson NR, Anton P, Bevers S, Welty R, Graner MW, Potter H. Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles. International Journal of Molecular Sciences. 2024; 25(7):3703. https://doi.org/10.3390/ijms25073703

Chicago/Turabian Style

Coughlan, Christina, Jared Lindenberger, Jeffrey G. Jacot, Noah R. Johnson, Paige Anton, Shaun Bevers, Robb Welty, Michael W. Graner, and Huntington Potter. 2024. "Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles" International Journal of Molecular Sciences 25, no. 7: 3703. https://doi.org/10.3390/ijms25073703

APA Style

Coughlan, C., Lindenberger, J., Jacot, J. G., Johnson, N. R., Anton, P., Bevers, S., Welty, R., Graner, M. W., & Potter, H. (2024). Specific Binding of Alzheimer’s Aβ Peptides to Extracellular Vesicles. International Journal of Molecular Sciences, 25(7), 3703. https://doi.org/10.3390/ijms25073703

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