Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity

Alzheimers Dement. 2024 Mar;20(3):1515-1526. doi: 10.1002/alz.13536. Epub 2023 Nov 29.

Abstract

Introduction: Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin-3 (Gal-3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal-3 levels in patients with FTD and assess its diagnostic potential.

Methods: We examined Gal-3 levels in brain, serum, and cerebrospinal fluid (CSF) samples of patients with FTD and controls. Multiple linear regressions between Gal-3 levels and other FTD markers were explored.

Results: Gal-3 levels were increased significantly in patients with FTD, mainly across brain tissue and CSF, compared to controls. Remarkably, Gal-3 levels were higher in cases with tau pathology than TAR-DNA Binding Protein 43 (TDP-43) pathology. Only MAPT mutation carriers displayed increased Gal-3 levels in CSF samples, which correlated with total tau and 14-3-3.

Discussion: Our findings underscore the potential of Gal-3 as a diagnostic marker for FTD, particularly in MAPT cases, and highlights the relation of Gal-3 with neuronal injury markers.

Keywords: C9orf72; CSF; GRN; MAPT; frontotemporal dementia; galectin-3; microglia; neuroinflammation.

MeSH terms

  • Biomarkers / cerebrospinal fluid
  • Brain / pathology
  • C9orf72 Protein / genetics
  • Frontotemporal Dementia* / diagnosis
  • Frontotemporal Dementia* / genetics
  • Galectin 3 / genetics
  • Galectin 3 / metabolism
  • Humans
  • Mutation / genetics
  • tau Proteins / cerebrospinal fluid

Substances

  • Galectin 3
  • tau Proteins
  • Biomarkers
  • C9orf72 Protein