The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer's disease but not those of sTREM2
Gispert, Juan Domingo (Universitat Pompeu Fabra)
Monté, Gemma C. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Suárez-Calvet, Marc (German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany)
Falcon, Carles (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Tucholka, Alan (Barcelonaβeta Brain Research Center (BBRC))
Rojas, Santiago (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Rami Gonzalez, Lorena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Sanchez-Valle, Raquel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Llado Plarrumani, Albert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Kleinberger, Gernot (Munich Cluster for Systems Neurology (SyNergy), Munich, Germany)
Haass, Christian (Munich Cluster for Systems Neurology (SyNergy), Munich, Germany)
Molinuevo, José Luis (Institut d'Investigacions Biomèdiques August Pi i Sunyer)

Data:	2016
Resum:	Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE ε4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimer's disease (AD). Brain magnetic resonance imaging (MRI) scans were acquired in 110 participants (49 control; 19 preclinical; 27 mild cognitive impairment [MCI] due to AD; 15 mild AD dementia) and CSF concentrations of YKL-40 and sTREM2 were determined. Differences in CSF biomarker concentrations and interactions in their association with gray-matter volume according to APOE ε4 status were sought after. Preclinical and MCI carriers showed higher YKL-40 levels. There was a significant interaction in the association between YKL-40 levels and gray-matter volume according to ε4 status. No similar effects could be detected for sTREM2 levels. Our findings are indicative of an increased astroglial activation in APOE ε4 carriers while both groups displayed similar levels of CSF AD core biomarkers.
Ajuts:	Instituto de Salud Carlos III PI14-00282
Nota:	Altres ajuts: This publication is part of the AETIONOMY project (Organising Mechanistic Knowledge about Neurodegenerative Diseases for the Improvement of Drug Development and Therapy) of the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AETIONOMY grant number 115568. Juan D. Gispert holds a "Ramón y Cajal" fellowship (RYC-2013-13054) and Lorena Rami is part of the "Programa de investigadores del sistema nacional Miguel Servet II" (CPII14/00023; IP: Lorena Rami). This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy), Cure Alzheimer's Fund, and MetLife Foundation Award (to Christian Haass).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Astrogliosis ; Microgliosis ; TREM2 ; Glial biomarkers ; Inflammation
Publicat a:	Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, Vol. 6 (december 2016) , p. 50-59, ISSN 2352-8729

DOI: 10.1016/j.dadm.2016.12.002
PMID: 28149943

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