Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer’s disease

Antonio Boza-serrano, Agathe Vrillon, Karolina Minta, Agnes Paulus, Lluís Camprubí-ferrer, Megg Garcia, Ulf Andreasson, Anna Antonell, Malin Wennström, Gunnar Gouras, Julien Dumurgier, Emmanuel Cognat, Laura Molina-porcel, Mircea Balasa, Javier Vitorica, Raquel Sánchez-valle, Claire Paquet, Jose Luis Venero, Kaj Blennow, Tomas Deierborg

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


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.
TidskriftActa Neuropathologica
StatusPublished - 2022 juli 27

Ämnesklassifikation (UKÄ)

  • Neurovetenskaper


Utforska forskningsämnen för ”Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer’s disease”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här