dc.creator | Boza Serrano, Antonio | es |
dc.creator | Vrillon, Agathe | es |
dc.creator | Minta, Karolina | es |
dc.creator | Paulus, Agnes | es |
dc.creator | Camprubí Ferrer, Lluís | es |
dc.creator | García, Megg | es |
dc.creator | Vitorica Ferrández, Francisco Javier | es |
dc.creator | Venero Recio, José Luis | es |
dc.creator | Deierborg, Tomas | es |
dc.date.accessioned | 2023-06-01T11:31:40Z | |
dc.date.available | 2023-06-01T11:31:40Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Boza Serrano, A., Vrillon, ., Minta, K., Paulus, A., Camprubí Ferrer, ., García, M.,...,Deierborg, T. (2022). Galectin-3 is elevated in CSF and is associated with A beta deposits and tau aggregates in brain tissue in Alzheimer's disease. Acta Neuropathologica, 144 (5), 843-859. https://doi.org/10.1007/s00401-022-02469-6. | |
dc.identifier.issn | 0001-6322 | es |
dc.identifier.issn | 1432-0533 | es |
dc.identifier.uri | https://hdl.handle.net/11441/146857 | |
dc.description.abstract | Galectin-3 (Gal-3) is a beta-galactosidase binding protein involved in microglial activation in the central nervous system
(CNS). We previously demonstrated the crucial deleterious role of Gal-3 in microglial activation in Alzheimer’s disease
(AD). Under AD conditions, Gal-3 is primarily expressed by microglial cells clustered around Aβ plaques in both human
and mouse brain, and knocking out Gal-3 reduces AD pathology in AD-model mice. To further unravel the importance of
Gal-3-associated infammation in AD, we aimed to investigate the Gal-3 infammatory response in the AD continuum. First,
we measured Gal-3 levels in neocortical and hippocampal tissue from early-onset AD patients, including genetic and sporadic
cases. We found that Gal-3 levels were signifcantly higher in both cortex and hippocampus in AD subjects. Immunohistochemistry revealed that Gal-3+microglial cells were associated with amyloid plaques of a larger size and more irregular
shape and with neurons containing tau-inclusions. We then analyzed the levels of Gal-3 in cerebrospinal fuid (CSF) from
AD patients (n=119) compared to control individuals (n=36). CSF Gal-3 levels were elevated in AD patients compared
to controls and more strongly correlated with tau (p-Tau181 and t-tau) and synaptic markers (GAP-43 and neurogranin)
than with amyloid-β. Lastly, principal component analysis (PCA) of AD biomarkers revealed that CSF Gal-3 clustered and
associated with other CSF neuroinfammatory markers, including sTREM-2, GFAP, and YKL-40. This neuroinfammatory component was more highly expressed in the CSF from amyloid-β positive (A+), CSF p-Tau181 positive (T+), and
biomarker neurodegeneration positive/negative (N+/−) (A+T+N+/−) groups compared to the A+T−N− group. Overall,
Gal-3 stands out as a key pathological biomarker of AD pathology that is measurable in CSF and, therefore, a potential target
for disease-modifying therapies involving the neuroinfammatory response. | es |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades de España RTI2018-098645-B-100 | es |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades, RTI2018-098645-B-100 y PID2021-124096OB-100 | es |
dc.description.sponsorship | Instituto de Salud Carlos III de España - 20/00448 | es |
dc.description.sponsorship | Fondos FEDER de la Unión Europea - PI18/01556 y PI21/00914 | es |
dc.description.sponsorship | Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía. España - P18-RT-1372 | es |
dc.format | application/pdf | es |
dc.format.extent | 17 p. | es |
dc.language.iso | eng | es |
dc.publisher | Springer | es |
dc.relation.ispartof | Acta Neuropathologica, 144 (5), 843-859. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Galectin-3 is elevated in CSF and is associated with A beta deposits and tau aggregates in brain tissue in Alzheimer's disease | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | RTI2018-098645-B-100 | es |
dc.relation.projectID | PID2021-124096OB-100 | es |
dc.relation.projectID | ISCiii 20/00448 | es |
dc.relation.projectID | PI18/01556 | es |
dc.relation.projectID | PI21/00914 | es |
dc.relation.projectID | P18-RT-1372 | es |
dc.relation.publisherversion | https://doi.org/10.1007/s00401-022-02469-6 | es |
dc.identifier.doi | 10.1007/s00401-022-02469-6 | es |
dc.journaltitle | Acta Neuropathologica | es |
dc.publication.volumen | 144 | es |
dc.publication.issue | 5 | es |
dc.publication.initialPage | 843 | es |
dc.publication.endPage | 859 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Instituto de Salud Carlos III | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Universidad de Sevilla | es |
dc.description.awardwinning | Premio Trimestral Publicación Científica Destacada de la US. Facultad de Farmacia | |