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

Boza-serrano, Antonio LU ; Vrillon, Agathe ; Minta, Karolina ; Paulus, Agnes LU ; Camprubí-ferrer, Lluís LU ; Garcia, Megg LU orcid ; Andreasson, Ulf ; Antonell, Anna ; Wennström, Malin LU and Gouras, Gunnar LU orcid , et al. (2022) In Acta Neuropathologica
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Neuropathologica
publisher
Springer
external identifiers
  • pmid:35895141
  • scopus:85135278573
ISSN
1432-0533
DOI
10.1007/s00401-022-02469-6
language
English
LU publication?
yes
id
dc1fedb1-9c3b-4557-b7d4-a2fab69b29a5
date added to LUP
2022-08-19 14:03:18
date last changed
2023-11-21 06:02:07
@article{dc1fedb1-9c3b-4557-b7d4-a2fab69b29a5,
  abstract     = {{Galectin-3 (Gal-3) is a beta-galactosidase binding protein involved in microglial activation in the central nervous system<br/>(CNS). We previously demonstrated the crucial deleterious role of Gal-3 in microglial activation in Alzheimer’s disease<br/>(AD). Under AD conditions, Gal-3 is primarily expressed by microglial cells clustered around Aβ plaques in both human<br/>and mouse brain, and knocking out Gal-3 reduces AD pathology in AD-model mice. To further unravel the importance of<br/>Gal-3-associated infammation in AD, we aimed to investigate the Gal-3 infammatory response in the AD continuum. First,<br/>we measured Gal-3 levels in neocortical and hippocampal tissue from early-onset AD patients, including genetic and sporadic<br/>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<br/>shape and with neurons containing tau-inclusions. We then analyzed the levels of Gal-3 in cerebrospinal fuid (CSF) from<br/>AD patients (n=119) compared to control individuals (n=36). CSF Gal-3 levels were elevated in AD patients compared<br/>to controls and more strongly correlated with tau (p-Tau181 and t-tau) and synaptic markers (GAP-43 and neurogranin)<br/>than with amyloid-β. Lastly, principal component analysis (PCA) of AD biomarkers revealed that CSF Gal-3 clustered and<br/>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<br/>biomarker neurodegeneration positive/negative (N+/−) (A+T+N+/−) groups compared to the A+T−N− group. Overall,<br/>Gal-3 stands out as a key pathological biomarker of AD pathology that is measurable in CSF and, therefore, a potential target<br/>for disease-modifying therapies involving the neuroinfammatory response.}},
  author       = {{Boza-serrano, Antonio and Vrillon, Agathe and Minta, Karolina and Paulus, Agnes and Camprubí-ferrer, Lluís and Garcia, Megg and Andreasson, Ulf and Antonell, Anna and Wennström, Malin and Gouras, Gunnar and Dumurgier, Julien and Cognat, Emmanuel and Molina-porcel, Laura and Balasa, Mircea and Vitorica, Javier and Sánchez-valle, Raquel and Paquet, Claire and Venero, Jose Luis and Blennow, Kaj and Deierborg, Tomas}},
  issn         = {{1432-0533}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{Springer}},
  series       = {{Acta Neuropathologica}},
  title        = {{Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1007/s00401-022-02469-6}},
  doi          = {{10.1007/s00401-022-02469-6}},
  year         = {{2022}},
}