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Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (<jats:italic>PRNP<\/jats:italic>), and iatrogenic CJD, as compared to healthy controls (HC) (AUC\u2009=\u20090.78\u20130.90) and neurological controls (AUC\u2009=\u20090.73\u20130.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer\u2019s disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are <jats:italic>PRNP<\/jats:italic> codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC\u2009=\u20090.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.<\/jats:p>","DOI":"10.1007\/s00401-021-02296-1","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T14:08:36Z","timestamp":1619014116000},"page":"841-859","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["TREM2 expression in the brain and biological fluids in prion diseases"],"prefix":"10.1007","volume":"141","author":[{"given":"Daniela","family":"Diaz-Lucena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Th\u00fcne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Villar-Piqu\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Eriton Gomes","family":"da Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"L\u00f3pez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol","family":"Andr\u00e9s-Benito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ladogana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Calero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Riggert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Pineau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Antonio","family":"del R\u00edo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Mar\u00edn-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Mar\u00eda","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc","family":"Llorens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"2296_CR1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3389\/fneur.2019.00280.eCollection","volume":"10","author":"A Abdelhak","year":"2019","unstructured":"Abdelhak A, Hottenrott T, Morenas-Rodr\u00edguez E, Su\u00e1rez-Calvet M, Zettl UK, Haass C et al (2019) Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker? 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KB has served as a consultant, on advisory boards, and on data monitoring committees for Abcam, Axon, Biogen, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Programme.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Brain tissue was obtained from the Institute of Neuropathology HUB-ICO-IDIBELL Biobank and the Hospital Clinic de Barcelona-IDIBAPS Neurological Tissue Bank following the Spanish legislation guidelines on this matter (Real Decreto de Biobancos 1716\/2011) and approval of the local ethics committees. CSF samples were collected at the following centres: (1) Clinical Dementia Centre and the National Reference Centre for CJD Surveillance at the University Medical Centre of G\u00f6ttingen (Germany); (2) Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Barcelona (Spain); (3) Multiple Sclerosis Unit Neurology Service, Bellvitge University Hospital, Hospitalet de Llobregat, Spain; (4) National Centre of Microbiology-Instituto de Salud Carlos III, Madrid, Spain; and (5) Istituto Superiore di Sanit\u00e0, Rome, Italy. Blood was collected at the Department of Transfusion Medicine (healthy controls) and at the Department of Neurology (sCJD cases) of the University Medical Centre G\u00f6ttingen (Germany) under standardized pre-analytical conditions.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human sample acquisition"}},{"value":"We conducted animal experiments in accordance with the Code for Methods and Welfare Considerations in Behavioural Research with Animals (Directive 2010\/63\/EU) and made every effort to minimize suffering. Experiments developed in the Centro de Investigaci\u00f3n en Sanidad Animal\u2013Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (Madrid, Spain) were evaluated by the Committee on the Ethics of Animal Experiments of the Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria and approved by the General Directorate of the Madrid Community Government (permit no. PROEX 094\/18).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal experimentation"}}]}}