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TREM2 expression in the brain and biological fuids in prion diseases.pdf (6.12 MB)

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2021-04-21

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cc by (c) Diaz Lucena et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177299

TREM2 expression in the brain and biological fluids in prion diseases

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Recurs relacionat

https://doi.org/10.1007/s00401-021-02296-1

Resum

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.

Matèries

Malalties per prions, Malaltia de Creutzfeldt-Jakob, Líquid cefalorraquidi

Matèries (anglès)

Prion diseases, Creutzfeldt-Jakob disease, Cerebrospinal fluid

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Col·leccions

Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

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. TREM2 expression in the brain and biological fluids in prion diseases. _Acta Neuropathologica_. 2021. Vol. 141, núm. 6, pàgs. 841-859. [consulta: 29 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/177299]

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