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Title: TREM2 expression in the brain and biological fluids in prion diseases
Author: Diaz Lucena, Daniela
Kruse, Niels
Thüne, Katrin
Schmitz, Matthias
Villar Piqué, Anna
Gomes da Cunha, Jose Eriton
Hermann, Peter
López Pérez, Óscar
Andrés Benito, Pol
Ladogana, Anna
Calero, Miguel
Vidal, Enric
Riggert, Joachim
Pineau, Hailey
Sim, Valerie
Zetterberg, Henrik
Blennow, Kaj
Río Fernández, José Antonio del
Marín Moreno, Alba
Espinosa, Juan Carlos
Torres, Juan María
Sánchez Valle, Raquel
Mollenhauer, Brit
Ferrer, Isidro (Ferrer Abizanda)
Zerr, Inga
Llorens Torres, Franc
Keywords: Malalties per prions
Malaltia de Creutzfeldt-Jakob
Líquid cefalorraquidi
Prion diseases
Creutzfeldt-Jakob disease
Cerebrospinal fluid
Issue Date: 21-Apr-2021
Publisher: Springer Nature
Abstract: 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.
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It is part of: Acta Neuropathologica, 2021, vol. 141, num. 6, p. 841-859
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Appears in Collections:Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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