TREM2 expression in the brain and biological fluids in prion diseases
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Autor/a
Diaz‑Lucena, Daniela
Kruse, Niels
Thüne, Katrin
Schmitz, Matthias
Villar‑Piqué, Anna
da Cunha, Jose Eriton Gomes
Hermann, Peter
López‑Pérez, Óscar
Andrés‑Benito, Pol
Ladogana, Anna
Calero, Miguel
Riggert, Joachim
Pineau, Hailey
Sim, Valerie
Zetterberg, Henrik
Blennow, Kaj
del Río, Jose Antonio
Marín‑Moreno, Alba
Espinosa, Juan Carlos
Torres, Juan María
Sánchez‑Valle, Raquel
Mollenhauer, Brit
Ferrer, Isidre
Zerr, Inga
Llorens, Franc
Fecha de publicación
2021-04-21ISSN
0001-6322
Resumen
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. 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 (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78–0.90) and neurological controls (AUC = 0.73–0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer’s disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP 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 = 0.80), 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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
19
Publicado por
Springer
Publicado en
Acta Neuropathologica
Citación
Diaz-Lucena, Daniela, Niels Kruse, Katrin Thüne, Matthias Schmitz, Anna Villar-Piqué, Jose Eriton Gomes da Cunha, and Peter Hermann et al. 2021. "TREM2 Expression In The Brain And Biological Fluids In Prion Diseases". Acta Neuropathologica 141 (6): 841-859. doi:10.1007/s00401-021-02296-1.
Número del acuerdo de la subvención
ISCIII/Programa Estatal de I+D+I orientada a los retos de la Sociedad/CP16-00041/ES/ /
ISCIII/Programa Estatal de I+D+I orientada a los retos de la sociedad/PI19-00144/ES/Desarrollo, validación e implementación de nuevos tests biomarcadores para demencias neurodegenerativas. Papel en diagnosis, prognosis y seguimiento de la enfermedad/
EC/INTERREG-POCTEFA/EU/ / /
EC/H2020/801370/EU/Beatriu de Pinos-3 Postdoctoral Programme/BP3
EC/H2020/681712/EU/Pathways to Alzheimer's disease/PATHAD
MICIU/Programa estatal de I+D+i orientada a los retos de la sociedad/RTI2018-099773-B-I00/ES/NUEVAS APROXIMACIONES PARA ENTENDER LAS FUNCIONES DE LA PRPC Y MIEMBROS SECRETABLES DE SEMAFORINAS DURANTE EL DESARROLLO DEL HIPOCAMPO Y EN NEUROTRANSMISION/
Program
Sanitat Animal
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