RT Journal Article
T1 Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer's disease.
A1 Boza-Serrano, Antonio
A1 Vrillon, Agathe
A1 Minta, Karolina
A1 Paulus, Agnes
A1 Camprubí-Ferrer, Lluís
A1 Garcia, Megg
A1 Andreasson, Ulf
A1 Antonell, Anna
A1 Wennström, Malin
A1 Gouras, Gunnar
A1 Dumurgier, Julien
A1 Cognat, Emmanuel
A1 Molina-Porcel, Laura
A1 Balasa, Mircea
A1 Vitorica, Javier
A1 Sánchez-Valle, Raquel
A1 Paquet, Claire
A1 Venero, Jose Luis
A1 Blennow, Kaj
A1 Deierborg, Tomas
AB 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 inflammation in AD, we aimed to investigate the Gal-3 inflammatory 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 significantly 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 fluid (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 neuroinflammatory markers, including sTREM-2, GFAP, and YKL-40. This neuroinflammatory 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 neuroinflammatory response.
YR 2022
FD 2022-07-27
LK http://hdl.handle.net/10668/19953
UL http://hdl.handle.net/10668/19953
LA en
DS RISalud
RD Apr 4, 2025