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Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms\/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients\u2019 plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.<\/jats:p>","DOI":"10.3390\/ijms23105598","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"5598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington\u2019s Disease and Human Blood Plasma"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-4172","authenticated-orcid":false,"given":"Hanadi","family":"Ananbeh","sequence":"first","affiliation":[{"name":"Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 27721 Libechov, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-9389","authenticated-orcid":false,"given":"Jaromir","family":"Novak","sequence":"additional","affiliation":[{"name":"Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 27721 Libechov, Czech Republic"},{"name":"Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-0727","authenticated-orcid":false,"given":"Stefan","family":"Juhas","sequence":"additional","affiliation":[{"name":"Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 27721 Libechov, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-6812","authenticated-orcid":false,"given":"Jana","family":"Juhasova","sequence":"additional","affiliation":[{"name":"Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 27721 Libechov, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-7155","authenticated-orcid":false,"given":"Jiri","family":"Klempir","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Katerinska 30, 12821 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-4002","authenticated-orcid":false,"given":"Kristyna","family":"Doleckova","sequence":"additional","affiliation":[{"name":"Department of 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