TREM2 expression in the brain and biological fluids in prion diseases
Diaz-Lucena, Daniela (Institut d'Investigació Biomèdica de Bellvitge)
Kruse, Niels (University Medical Center Göttingen. Institute of Neuropathology)
Thüne, Katrin (University Medical Center Göttingen. Department of Neurology)
Schmitz, Matthias (German Center for Neurodegenerative Diseases)
Villar-Piqué, Anna (Institut d'Investigació Biomèdica de Bellvitge)
da Cunha, Jose Eriton Gomes (Universidade Federal de Pernambuco. Keizo Asami Laboratory)
Hermann, Peter (University Medical Center Göttingen. Department of Neurology)
López-Pérez, Óscar (Institut d'Investigació Biomèdica de Bellvitge)
Andrés-Benito, P (Institut d'Investigació Biomèdica de Bellvitge)
Ladogana, Anna (Istituto Superiore Di Sanità. Department of Neurosciences)
Calero, Miguel (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Vidal Barba, Enric (Institut de Recerca i Tecnologia Agroalimentàries)
Riggert, Joachim (University Medical School. Department of Transfusion Medicine)
Pineau, Hailey (University of Alberta. Department of Medicine-Division of Neurology)
Sim, Valerie (University of Alberta. Department of Medicine-Division of Neurology)
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit))
Blennow, Kaj (Sahlgrenska University Hospital. Clinical Neurochemistry Laboratory)
Del Rio, Jose Antonio (Universitat de Barcelona. Institut de Neurociències)
Marín-Moreno, Alba (Centro de Investigación en Sanidad Animal. CISA-INIA)
Espinosa, Juan Carlos (Centro de Investigación en Sanidad Animal. CISA-INIA)
Torres, Juan María (Centro de Investigación en Sanidad Animal. CISA-INIA)
Sanchez-Valle, Raquel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Mollenhauer, Brit (University Medical Centre Göttingen. Department of Neurology)
Ferrer, Isidro (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Zerr, Inga (German Center for Neurodegenerative Diseases)
Llorens, Franc (University Medical Center Göttingen. Department of Neurology)

Data:	2021
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 signifcantly 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, neuroflament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fuids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratifcation, and disease monitoring.
Ajuts:	Instituto de Salud Carlos III CP16/00041 Instituto de Salud Carlos III PI19/00144 Ministerio de Ciencia e Innovación RTI2018-099773-B-I00
Nota:	The online version contains supplementary material available at 10.1007/s00401-021-02296-1.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	TREM2 ; Prion diseases ; Creutzfeldt-Jakob disease ; Microglia ; Cerebrospinal fluid ; Plasma
Publicat a:	Acta Neuropathologica, Vol. 141 (april 2021) , p. 841-859, ISSN 1432-0533

DOI: 10.1007/s00401-021-02296-1
PMID: 33881612

19 p, 6.1 MB

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