Galectin-3 is elevated in CSF and is associated with A beta deposits and tau aggregates in brain tissue in Alzheimer's disease
|Author/s||Boza Serrano, Antonio
Camprubí Ferrer, Lluís
Vitorica Ferrández, Francisco Javier
Venero Recio, José Luis
|Department||Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular|
|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 ...
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.
|Funding agencies||Ministerio de Ciencia e Innovación (MICIN). España
Instituto de Salud Carlos III
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Junta de Andalucía
Universidad de Sevilla
|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.|