CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals
Cerebrospinal fluid (CSF) YKL40 and sTREM2 are astroglial and microglial activity biomarkers, respectively. We assessed whether CSF YKL40 and sTREM2 baseline levels are associated with longitudinal brain volume and diffusivity changes in cognitively unimpaired adults. Two brain MRI scans of 36 parti...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/45110 |
| Acceso en línea: | http://hdl.handle.net/10230/45110 http://dx.doi.org/10.1016/j.nicl.2019.101801 |
| Access Level: | acceso abierto |
| Palabra clave: | Longitudinal analysis Mean diffusivity Preclinical Alzheimer&apos s disease TREM2 YKL40 |
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| dc.title.none.fl_str_mv |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| title |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| spellingShingle |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals Falcón, Carles Longitudinal analysis Mean diffusivity Preclinical Alzheimer&apos s disease TREM2 YKL40 |
| title_short |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| title_full |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| title_fullStr |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| title_full_unstemmed |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| title_sort |
CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals |
| dc.creator.none.fl_str_mv |
Falcón, Carles Monté-Rubio, Gemma C. Grau, Oriol (Grau Rivera) Suárez-Calvet, Marc Sánchez Valle, Raquel Rami, Lorena Bosch, Beatriz Haass, Christian Gispert, Juan Domingo Molinuevo, José Luis |
| author |
Falcón, Carles |
| author_facet |
Falcón, Carles Monté-Rubio, Gemma C. Grau, Oriol (Grau Rivera) Suárez-Calvet, Marc Sánchez Valle, Raquel Rami, Lorena Bosch, Beatriz Haass, Christian Gispert, Juan Domingo Molinuevo, José Luis |
| author_role |
author |
| author2 |
Monté-Rubio, Gemma C. Grau, Oriol (Grau Rivera) Suárez-Calvet, Marc Sánchez Valle, Raquel Rami, Lorena Bosch, Beatriz Haass, Christian Gispert, Juan Domingo Molinuevo, José Luis |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Longitudinal analysis Mean diffusivity Preclinical Alzheimer&apos s disease TREM2 YKL40 |
| topic |
Longitudinal analysis Mean diffusivity Preclinical Alzheimer&apos s disease TREM2 YKL40 |
| description |
Cerebrospinal fluid (CSF) YKL40 and sTREM2 are astroglial and microglial activity biomarkers, respectively. We assessed whether CSF YKL40 and sTREM2 baseline levels are associated with longitudinal brain volume and diffusivity changes in cognitively unimpaired adults. Two brain MRI scans of 36 participants (57 to 78-years old, 12 male) were acquired in a 2-year interval. Aβ42, p-tau, YKL40 and sTREM2 concentrations in CSF were determined at baseline. We calculated gray and white matter volume changes per year maps (ΔGM and ΔWM, respectively) by means of longitudinal pairwise registration, and mean diffusivity variation per year (ΔMD) by subtraction. We checked voxel-wise for associations between ΔGM, ΔWM and ΔMD and baseline CSF level of YKL40 and sTREM2 and verified to what extent these associations were modulated by age (YKL40xAGE and sTREM2xAGE interactions). We found a positive association between ΔGM and YKL40 in the left inferior parietal region and no association between sTREM2 and ΔGM. Negative associations were also observed between ΔGM and YKL40xAGE (bilateral frontal areas, left precuneus and left postcentral and supramarginal gyri) and sTREM2xAGE (bilateral temporal and frontal cortex, putamen and left middle cingulate gyrus). We found negative associations between ΔWM and YKL40xAGE (bilateral superior longitudinal fasciculus) and sTREM2xAGE (bilateral superior longitudinal fasciculus, left superior corona radiata, retrolenticular external capsule and forceps minor, among other regions) but none between ΔWM and neither YKL40 nor sTREM2. ΔMD was positively correlated with YKL40 in right orbital region and negatively with sTREM2 in left lingual gyrus and precuneus. In addition, significant associations were found between ΔMD and YKL40xAGE (tail of left hippocampus and surrounding areas and right anterior cingulate gyrus) and sTREM2xAGE (right superior temporal gyrus). Areas showing statistically significant differences were disjoint in analyses involving YKL40 and sTREM2. These results suggest that glial biomarkers exert a relevant and distinct influence in longitudinal brain macro- and microstructural changes in cognitively unimpaired adults, which appears to be modulated by age. In younger subjects increased glial markers (both YKL40 and sTREM2) predict a better outcome, as indicated by a decrease in ΔGM and ΔWM and an increase in ΔMD, whereas in older subjects this association is inverted and higher levels of glial markers are associated with a poorer neuroimaging outcome. |
| publishDate |
2019 |
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2019 2020 2020 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10230/45110 http://dx.doi.org/10.1016/j.nicl.2019.101801 |
| url |
http://hdl.handle.net/10230/45110 http://dx.doi.org/10.1016/j.nicl.2019.101801 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Neuroimage Clin. 2019; 23:101801 info:eu-repo/grantAgreement/EC/FP7/115568 info:eu-repo/grantAgreement/EC/H2020/752310 |
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http://creativecommons.org/licenses/BY-NC-ND/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/BY-NC-ND/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individualsFalcón, CarlesMonté-Rubio, Gemma C.Grau, Oriol (Grau Rivera)Suárez-Calvet, MarcSánchez Valle, RaquelRami, LorenaBosch, BeatrizHaass, ChristianGispert, Juan DomingoMolinuevo, José LuisLongitudinal analysisMean diffusivityPreclinical Alzheimer&aposs diseaseTREM2YKL40Cerebrospinal fluid (CSF) YKL40 and sTREM2 are astroglial and microglial activity biomarkers, respectively. We assessed whether CSF YKL40 and sTREM2 baseline levels are associated with longitudinal brain volume and diffusivity changes in cognitively unimpaired adults. Two brain MRI scans of 36 participants (57 to 78-years old, 12 male) were acquired in a 2-year interval. Aβ42, p-tau, YKL40 and sTREM2 concentrations in CSF were determined at baseline. We calculated gray and white matter volume changes per year maps (ΔGM and ΔWM, respectively) by means of longitudinal pairwise registration, and mean diffusivity variation per year (ΔMD) by subtraction. We checked voxel-wise for associations between ΔGM, ΔWM and ΔMD and baseline CSF level of YKL40 and sTREM2 and verified to what extent these associations were modulated by age (YKL40xAGE and sTREM2xAGE interactions). We found a positive association between ΔGM and YKL40 in the left inferior parietal region and no association between sTREM2 and ΔGM. Negative associations were also observed between ΔGM and YKL40xAGE (bilateral frontal areas, left precuneus and left postcentral and supramarginal gyri) and sTREM2xAGE (bilateral temporal and frontal cortex, putamen and left middle cingulate gyrus). We found negative associations between ΔWM and YKL40xAGE (bilateral superior longitudinal fasciculus) and sTREM2xAGE (bilateral superior longitudinal fasciculus, left superior corona radiata, retrolenticular external capsule and forceps minor, among other regions) but none between ΔWM and neither YKL40 nor sTREM2. ΔMD was positively correlated with YKL40 in right orbital region and negatively with sTREM2 in left lingual gyrus and precuneus. In addition, significant associations were found between ΔMD and YKL40xAGE (tail of left hippocampus and surrounding areas and right anterior cingulate gyrus) and sTREM2xAGE (right superior temporal gyrus). Areas showing statistically significant differences were disjoint in analyses involving YKL40 and sTREM2. These results suggest that glial biomarkers exert a relevant and distinct influence in longitudinal brain macro- and microstructural changes in cognitively unimpaired adults, which appears to be modulated by age. In younger subjects increased glial markers (both YKL40 and sTREM2) predict a better outcome, as indicated by a decrease in ΔGM and ΔWM and an increase in ΔMD, whereas in older subjects this association is inverted and higher levels of glial markers are associated with a poorer neuroimaging outcome.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115568, resources of which are composed of financial contribution from the European Union‘s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. 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). Marc Suárez-Calvet was awarded with an AFTD Biomarkers Initiative awards from the The Association for Frontotemporal Degeneration and receives funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310. 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). The present communication reflects the authors' view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.Elsevier202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45110http://dx.doi.org/10.1016/j.nicl.2019.101801reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNeuroimage Clin. 2019; 23:101801info:eu-repo/grantAgreement/EC/FP7/115568info:eu-repo/grantAgreement/EC/H2020/752310© 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).http://creativecommons.org/licenses/BY-NC-ND/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/451102026-06-12T07:21:37Z |
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15,81155 |