CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline
Suárez-Calvet, Marc (Ludwig-Maximilians-Universität München)
Capell, Anja (Ludwig-Maximilians-Universität München)
Araque Caballero, Miguel Ángel (Ludwig-Maximilians-Universität München)
Morenas-Rodríguez, Estrella (Universitat Autònoma de Barcelona)
Fellerer, Katrin (Ludwig-Maximilians-Universität München)
Franzmeier, Nicolai (Ludwig-Maximilians-Universität München)
Kleinberger, Gernot (Munich Cluster for Systems Neurology (SyNergy))
Eren, Erden (Dokuz Eylul University, Turkey)
Deming, Yuetiva (Washington University School of Medicine)
Piccio, Laura (Washington University School of Medicine)
Karch, Celeste M. (Washington University School of Medicine)
Cruchaga, Carlos (Washington University School of Medicine)
Paumier, Katrina (Washington University School of Medicine)
Bateman, Randall J. (Washington University School of Medicine)
Fagan, Anne M. (Washington University School of Medicine)
Morris, John C. (Washington University School of Medicine)
Levin, Johannes (Ludwig-Maximilians-Universität München)
Danek, Adrian (Ludwig-Maximilians-Universität München)
Jucker, Mathias (University of Tübingen)
Masters, Colin L. (University of Melbourne)
Rossor, Martin N. (UCL Institute of Neurology (Regne Unit))
Ringman, John M. (University of Southern California)
Shaw, Leslie M. (University of Pennsylvania)
Trojanowski, John Q.. (University of Pennsylvania)
Weiner, Michael (University of California at San Francisco)
Ewers, Michael (Ludwig-Maximilians-Universität München)
Haass, Christian (Munich Cluster for Systems Neurology (SyNergy))

Date:	2018
Abstract:	Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether expression is changed in a disease severity-specific manner in . We measured in cerebrospinal fluid (CSF) in two of the best-characterized patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of causing dominant mutations, cross-sectionally assessed increased over the course of the disease and significantly differed from non-carriers 10 years before the expected symptom onset. In late-onset , higher was associated with more advanced disease stages and cognitive impairment. Higher was associated with higher soluble 2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although is not a diagnostic biomarker for , it may together with 2 reflect microglial activation during the disease.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; Biomarker ; Microglia ; Progranulin ; TREM2 ; Diagnostic Imaging ; Neuroscience
Published in:	EMBO Molecular Medicine, Vol. 10 (november 2018) , ISSN 1757-4684

DOI: 10.15252/emmm.201809712
PMID: 30482868

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