{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:27:55Z","timestamp":1792805275037,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Colorado Alzheimer\u2019s and Cognition Center (CUACC)","id":[{"id":"https:\/\/ror.org\/00jc20583","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s 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 A\u03b242, defines when people are on the AD continuum. Interestingly, as AD progresses, less A\u03b242 is detectable in the plasma, a phenomenon thought to result from A\u03b2 becoming more aggregated in the brain and less A\u03b242 and A\u03b240 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 \u201ccargos\u201d of bioactive molecules (e.g., proteins, nucleic acids, lipids, metabolites) that dynamically reflect changes in the cells from which they are secreted. While A\u03b242 and A\u03b240 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 A\u03b2 and EVs, we used isothermal titration calorimetry (ITC) and discovered that A\u03b242 and A\u03b240 bind to EVs in a manner that is sequence specific, saturable, and endothermic. In addition, A\u03b2 incubation with EVs overnight yielded larger amounts of bound A\u03b2 peptide that was fibrillar in structure. These findings point to a specific amyloid\u2013EV 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.<\/jats:p>","DOI":"10.3390\/ijms25073703","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:34:58Z","timestamp":1711452898000},"page":"3703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Specific Binding of Alzheimer\u2019s A\u03b2 Peptides to Extracellular Vesicles"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-7056","authenticated-orcid":false,"given":"Christina","family":"Coughlan","sequence":"first","affiliation":[{"name":"University of Colorado Alzheimer\u2019s 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Lindenberger","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Duke Human Vaccine Institute, Duke University, 2 Genome Ct., Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-5055","authenticated-orcid":false,"given":"Jeffrey G.","family":"Jacot","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Colorado Anschutz Medical Campus, 13001 E. 17th Pl, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer\u2019s 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Anton","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer\u2019s 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Bevers","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robb","family":"Welty","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-0257","authenticated-orcid":false,"given":"Michael W.","family":"Graner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Colorado Anschutz Medical Campus, 13001 E. 17th Pl, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-2516","authenticated-orcid":false,"given":"Huntington","family":"Potter","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer\u2019s 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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. 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