What Is Galectin-3? How Is It Implicated in Dementia — and What About TB006?
Last Updated: November 2025
Galectin-3 is an inflammatory protein increasingly linked to neurodegeneration and cognitive decline. In this FAQ, Dr. Jessica Knape of HealthSpan Internal Medicine in Boulder, CO explains its role in dementia—and explores TB006, a novel therapeutic targeting Galectin-3 that shows potential in early clinical trials
Overview
Galectin-3 is a lectin (carbohydrate-binding protein) that becomes elevated in brain injury, microglial activation, and neuroinflammation.
In dementia (especially Alzheimer’s disease), Galectin-3 is linked to formation of amyloid-β plaques, tau pathology, and ongoing inflammation.
TB006 is a humanized monoclonal antibody under investigation that targets Galectin-3 and is available in limited compassionate-use or expanded-access programs.
While promising, TB006 is not FDA-approved for dementia; any use must be under supervised protocols with full informed consent.
Galectin-3 testing or inhibition is not yet part of standard dementia care—but the research is advancing, and keeping abreast of developments is wise.
Summary
Galectins are a family of proteins that bind certain sugars (β-galactosides) and participate in cellular processes including cell adhesion, immune activation, and inflammation. Among them, Galectin-3 (Gal-3) has emerged as a key molecule in brain injury responses, neuroinflammation, and possibly neurodegeneration.
At HealthSpan Internal Medicine in Boulder, CO, we take an evidence-based view: Galectin-3 may be a biomarker and a therapeutic target in dementia, but current therapies remain investigational.
What Is Galectin-3 and What Does It Do in the Brain?
Galectin-3 is encoded by the LGALS3 gene and is found in many cell types: microglia (brain immune cells), astrocytes, endothelial cells, and macrophages. Important functions include:
Activation of microglia (brain’s resident immune cells) in response to injury or stress.
Modulation of inflammatory signaling via TLR4, IGF-R1 and other pathways.
Binding to β-galactoside sugars on cell surfaces, clumping of glycosylated proteins, and possible cross-linking of extracellular molecules.
In the brain, Gal-3 expression increases after ischemia, trauma, or cell damage—suggesting a role in repair but also potentially in chronic damage when activation becomes prolonged.
Thus, Galectin-3 appears to act as a gatekeeper between acute injury repair and chronic inflammation: when controlled, it may help clean up damage; when persistent, it may promote harmful processes.
How Is Galectin-3 Implicated in Dementia?
Multiple lines of evidence link Galectin-3 to cognitive decline and dementia:
1. Elevated Levels in Dementia Patients
Studies show higher Gal-3 levels in the cerebrospinal fluid (CSF) or serum of patients with Alzheimer’s disease or frontotemporal dementia compared with controls.
2. Promotion of Amyloid-β and Tau Pathology
Research indicates Galectin-3 may bind to amyloid-β (Aβ) oligomers and tau protein, promoting aggregation into plaques and tangles—key neuropathologic hallmarks of Alzheimer’s disease.
3. Microglial Activation & Neuroinflammation
Galectin-3 regulates microglial activation: in models where Gal-3 is genetically knocked out, microglial inflammation and neuronal damage after ischemia decrease. Chronic microglial activation is associated with neurodegeneration.
4. Biomarker of Poor Outcome
High Gal-3 has been tied to worse outcomes in stroke, neurodegeneration, and other brain injuries, suggesting that elevated Gal-3 may signal a “persistent injury / repair mode” that is harmful over time.
5. Possible Therapeutic Target
Because of its role upstream of Aβ/tau aggregation and inflammation, Galectin-3 is being explored as a target for modifying disease progression rather than simply treating symptoms.
What Is TB006? A Galectin-3 Targeting Therapy
TB006 is an investigational drug developed by TrueBinding, Inc.. Key points:
It is a humanized monoclonal antibody designed to bind and inhibit Galectin-3.
In preclinical Alzheimer’s disease models, TB006 blocked Galectin-3, reduced Aβ and tau aggregation, decreased neuroinflammation, and improved cognition and neuronal survival.
Early human trials (phase 1b/2a) in dementia patients have reported improvements in cognitive and functional endpoints; an open-label extension reported ~50% of participants showing stabilization or improvement after 3 months or more.
TB006 is not yet FDA-approved for Alzheimer’s or dementia. It is available only via clinical trials or expanded access (compassionate use) for eligible patients.
Because this is a novel target, long-term safety, optimal dosing, duration of benefit, and applicability to diverse dementia subtypes remain under investigation.
How Might Galectin-3 Inhibition Help Dementia Patients?
By targeting Galectin-3, therapies like TB006 may influence multiple harmful pathways in dementia:
Reduce Aβ/tau aggregation — by blocking Galectin-3’s binding role, fewer plaques/tangles may form, and existing oligomers may dissolve.
Lower microglial over-activation — reducing chronic brain inflammation helps protect neurons and synapses.
Improve clearance and repair — by shifting microglial phenotypes from “pro-inflammatory” to “repair/regenerative,” brain resilience might improve.
Address multiple dementia mechanisms — because Galectin-3 acts upstream of both proteinopathy and inflammation, it may be relevant beyond just Alzheimer’s disease (e.g., frontotemporal dementia, vascular dementia).How Might Galectin-3 Inhibition Help Dementia Patients?
By targeting Galectin-3, therapies like TB006 may influence multiple harmful pathways in dementia:
Reduce Aβ/tau aggregation — by blocking Galectin-3’s binding role, fewer plaques/tangles may form, and existing oligomers may dissolve.
Lower microglial over-activation — reducing chronic brain inflammation helps protect neurons and synapses.
Improve clearance and repair — by shifting microglial phenotypes from “pro-inflammatory” to “repair/regenerative,” brain resilience might improve.
Address multiple dementia mechanisms — because Galectin-3 acts upstream of both proteinopathy and inflammation, it may be relevant beyond just Alzheimer’s disease (e.g., frontotemporal dementia, vascular dementia).
Sources
Alzheimer's disease: Is there a role for galectins? - PubMed
TrueBinding Receives FDA Meeting for Accelerated TB006 Alzheimer’s Pathway - BioSpace
Galectin-3: A Promising Target in the Fight Against Alzheimer's Disease - GW Medicine
Galectin-3 Involvement in Cognitive Processes for New Therapeutic Considerations - Frontiers
Medically reviewed by
Dr. Jessica Knape, MD, MA Board Certified in Internal Medicine and Integrative and Holistic Medicine
Healthspan Internal Medicine — serving patients in Boulder, CO
Book a Discovery Call | About Dr. Knape
This content is for educational purposes and does not replace personalized medical advice.
