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We were interested in confirming HERVK overexpression in the ALS brain, its use as an accessory diagnostic marker for ALS, and its potential interplay with neuroinflammation. Using qPCR to analyze HERVK expression in peripheral blood mononuclear cells (PBMCs) and in postmortem brain samples from ALS patients, no significant differences were observed between patients and control subjects. By contrast, we report alterations in the expression patterns of specific HERVK copies, especially in the brainstem. Out of 27 HERVK copies sampled, the relative expression of 17 loci was &gt;1.2-fold changed in samples from ALS patients. In particular, the relative expression of two HERVK copies (Chr3-3 and Chr3-5) was significantly different in brainstem samples from ALS patients compared with controls. Further qPCR analysis of inflammation markers in brain samples revealed a significant increase in NLRP3 levels, while TNFA, IL6, and GZMB showed slight decreases. We cannot confirm global HERVK overexpression in ALS, but we can report the ALS-specific overexpression of selected HERVK copies in the ALS brain. Our data are compatible with the requirement for better patient stratification and support the potential importance of particular HERVK copies in ALS.<\/jats:p>","DOI":"10.3390\/ijms25031549","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T08:56:01Z","timestamp":1706259361000},"page":"1549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-4318","authenticated-orcid":false,"given":"Laura","family":"Moreno-Martinez","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Biochemistry (LAGENBIO), Faculty of Veterinary, University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas, 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Isabel","family":"Guill\u00e9n-Antonini","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[{"name":"NEMO (NEuroMuscular Omnicentre) Clinical Center, Fondazione Serena Onlus, 20162 Milan, Italy"},{"name":"Neurorehabilitation Department of Milano Institute, Istituti Clinici Scientifici Maugeri IRCCS, 20138 Milan, Italy"},{"name":"Medical Genetics Unit, Department of Laboratory Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tarlarini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Laboratory Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, 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