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

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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 (författare): Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,Hospital Clínic of Barcelona,University Hospital Virgen del Rocío

Vrillon, Agathe (författare): Université Paris Cité

Minta, Karolina (författare): University of Gothenburg

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Paulus, Agnes (författare): Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups

Camprubí-ferrer, Lluís (författare): Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups

Garcia, Megg (författare): Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups

Andreasson, Ulf (författare): University of Gothenburg,Sahlgrenska University Hospital

Antonell, Anna (författare): University of Barcelona

Wennström, Malin (författare): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups

Gouras, Gunnar (författare): Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups

Dumurgier, Julien (författare): Université Paris Cité

Cognat, Emmanuel (författare): Université Paris Cité

Molina-porcel, Laura (författare): University of Barcelona,Hospital Clínic of Barcelona

Balasa, Mircea (författare): Hospital Clínic of Barcelona,University of Barcelona

Vitorica, Javier (författare): CIBER Enfermedades Neurodegenerativas (CIBERNED),University Hospital Virgen del Rocío

Sánchez-valle, Raquel (författare): Hospital Clínic of Barcelona,University of Barcelona

Paquet, Claire (författare): Université Paris Cité

Venero, Jose Luis (författare): University of Seville,University Hospital Virgen del Rocío

Blennow, Kaj (författare): University of Gothenburg,Sahlgrenska University Hospital

Deierborg, Tomas (författare): Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups

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(creator_code:org_t)

2022-07-27
2022
Engelska.
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322.

Relaterad länk:: http://dx.doi.org/10... (free); visa fler...; https://lup.lub.lu.s...; https://doi.org/10.1...; visa färre...

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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 humanand mouse brain, and knocking out Gal-3 reduces AD pathology in AD-model mice. To further unravel the importance ofGal-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 sporadiccases. 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 irregularshape and with neurons containing tau-inclusions. We then analyzed the levels of Gal-3 in cerebrospinal fuid (CSF) fromAD patients (n=119) compared to control individuals (n=36). CSF Gal-3 levels were elevated in AD patients comparedto 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 andassociated 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+), andbiomarker 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 targetfor disease-modifying therapies involving the neuroinfammatory response.

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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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

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