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However, there is limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, nano-sized extracellular\n                    <jats:italic>vesicles<\/jats:italic>\n                    , in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200921) and healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916), and quantified exosomal HERV-K\n                    <jats:italic>gag<\/jats:italic>\n                    ,\n                    <jats:italic>env<\/jats:italic>\n                    , and\n                    <jats:italic>pol<\/jats:italic>\n                    transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome-enriched reference genes. HERV-K\n                    <jats:italic>pol<\/jats:italic>\n                    expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.037\u20130.051).\n                    <jats:italic>env<\/jats:italic>\n                    and\n                    <jats:italic>gag<\/jats:italic>\n                    also showed increased expression, though with greater variability. Normalization to the exosome-specific gene\n                    <jats:italic>SOD2<\/jats:italic>\n                    provided the most consistent signal. These findings suggest that exosomal HERV-K transcripts, particularly\n                    <jats:italic>pol<\/jats:italic>\n                    , could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV-K\u2013targeted ALS trials. This work establishes proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration and supports further investigation of liquid biopsy approaches in ALS precision medicine.\n                  <\/jats:p>","DOI":"10.1186\/s12868-026-01014-5","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:16:53Z","timestamp":1783768613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis"],"prefix":"10.1186","volume":"27","author":[{"given":"Triparna","family":"Roy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Ramesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Aisha Ahmad","family":"Nizam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Tandiono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khuloud T.","family":"Al-Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Al-Chalabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Iacoangeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-9831","authenticated-orcid":false,"given":"Ahmad","family":"Al Khleifat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"issue":"22","key":"1014_CR1","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","volume":"344","author":"LP Rowland","year":"2001","unstructured":"Rowland LP, Shneider NA. 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Newly collected clinical data were anonymised and handled in accordance with GDPR and institutional guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Informed consent Statement"}},{"value":"AA-C declares contracts with the MRC, NIHR and Darby Rimmer Foundation; consulting fees from Amylyx, Apellis, Biogen, Brainstorm, Clene Therapeutics, Cytokinetics, GenieUs, GSK, Lilly, Mitsubishi Tanabe Pharma, Novartis, OrionPharma, Quralis, Sano, and Sanofi). AAK declares contracts with the MRC ((MR\/Z505705\/1), the Motor Neurone Disease Association (MNDA), National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre, Amyotrophic Lateral Sclerosis (ALS) Association Milton Safenowitz Research Fellowship, Darby Rimmer MND Foundation, LifeArc, and the Dementia Consortium; equipment by NIHR Maudsley Biomedical Research Centre; and consulting fees from the UK National Endowment for Science, Technology and the Arts (NESTA).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}