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We previously demonstrated the crucial deleterious role of Gal-3 in microglial activation in Alzheimer\u2019s disease (AD). Under AD conditions, Gal-3 is primarily expressed by microglial cells clustered around A\u03b2 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+\u2009microglial 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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009119) compared to control individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200936). CSF\u00a0Gal-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-\u03b2. Lastly, principal component analysis (PCA) of AD biomarkers revealed that CSF\u00a0Gal-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-\u03b2 positive (A+), CSF\u00a0p-Tau181 positive (T+), and biomarker neurodegeneration positive\/negative (N+\/\u2212) (A\u2009+\u2009T\u2009+\u2009N+\/\u2212) groups compared to the A\u2009+\u2009T\u2212N\u2212 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.\n                  <\/jats:p>","DOI":"10.1007\/s00401-022-02469-6","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T04:49:40Z","timestamp":1659156580000},"page":"843-859","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Galectin-3 is elevated in CSF and is associated with A\u03b2 deposits and tau aggregates in brain tissue in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-2486","authenticated-orcid":false,"given":"Antonio","family":"Boza-Serrano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Vrillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Minta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Paulus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Camprub\u00ed-Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megg","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Andreasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Antonell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Wennstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Gouras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Dumurgier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Cognat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mircea","family":"Balasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Vitorica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Paquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Venero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Deierborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"2469_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/j.jalz.2018.05.004","volume":"14","author":"ML Alosco","year":"2018","unstructured":"Alosco ML, Tripodis Y, Fritts NG, Heslegrave A, Baugh CM, Conneely S et al (2018) Cerebrospinal fluid tau, Abeta, and sTREM2 in former national football league players: modeling the relationship between repetitive head impacts, microglial activation, and neurodegeneration. 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