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

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  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Monté-Rubio, Gemma C.
  • dc.contributor.author Suárez-Calvet, Marc
  • dc.contributor.author Falcon, Carles
  • dc.contributor.author Tucholka, Alan
  • dc.contributor.author Rojas, Santiago
  • dc.contributor.author Rami, Lorena
  • dc.contributor.author Sánchez Valle, Raquel
  • dc.date.accessioned 2024-01-16T07:01:40Z
  • dc.date.available 2024-01-16T07:01:40Z
  • dc.date.issued 2016
  • dc.description.abstract Introduction. 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). Methods. 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. Results. 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. Discussion. Our findings are indicative of an increased astroglial activation in APOE ε4 carriers while both groups displayed similar levels of CSF AD core biomarkers.
  • dc.description.sponsorship 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. This work was also partially financed by grant to Dr. Albert Lladó (PI14/00282) from the Spanish Ministry of Economy and Competitiveness ISCIII and cofunded by the European Regional Development Fund (ERDF). 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).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gispert JD, Monté GC, Suárez‐Calvet M, Falcon C, Tucholka A, Rojas S, et al. 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. Alz & Dem Diag Ass & Dis Mo. 2016 Dec 22;6(1):50-9. DOI: 10.1016/j.dadm.2016.12.002
  • dc.identifier.doi http://dx.doi.org/10.1016/j.dadm.2016.12.002
  • dc.identifier.issn 2352-8729
  • dc.identifier.uri http://hdl.handle.net/10230/58712
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 2016 Dec 22;6(1):50-9
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115568
  • dc.rights © 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Astrogliosis
  • dc.subject.keyword Microgliosis
  • dc.subject.keyword TREM2
  • dc.subject.keyword Glial biomarkers
  • dc.subject.keyword Inflammation
  • dc.title 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
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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