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Related Experiment Video

Updated: Jul 7, 2026

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Published on: November 9, 2018

Inflammatory alterations mediate tau-associated neurodegeneration.

Patrick J Lao¹, Seonjoo Lee², Daniel Talmasov¹

¹Taub Institute for Research on Alzheimer's Disease and the Aging Brain, G.H. Sergievsky Center, Department of Neurology, Columbia University Irving Medical Center, NewYork, NY 10032, USA.

Brain Communications

|July 6, 2026

Summary

Microglia activation, measured by 18 kDa translocator PET, is linked to tau pathology in Alzheimer's disease. Targeting glia may help treat tau-associated neurodegeneration.

Keywords:

TSPO PET amyloid microglia neurodegeneration tau

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Area of Science:

Neuroscience
Neuropathology
Radiology

Background:

Microglia play a crucial role in brain homeostasis but can become chronically pro-inflammatory in Alzheimer's disease (AD), potentially exacerbating pathology.
Understanding the role of microglia in AD pathogenesis is essential for developing effective therapeutic strategies.

Purpose of the Study:

To investigate the relationship between microglia density, measured by 18 kDa translocator PET, and the distribution of amyloid, tau, and neurodegeneration biomarkers in cognitively impaired individuals.
To determine if microglia density is associated with tau pathology and if it mediates the relationship between amyloid, tau, and neurodegeneration.

Main Methods:

Utilized positron emission tomography (PET) imaging to quantify amyloid (Florbetaben), tau (MK6240), and microglia density (ER176, 18 kDa translocator) in 46 participants (21 cognitively unimpaired, 25 cognitively impaired).
Structural MRI was used to assess grey matter volume. Biomarkers were analyzed in 13 predefined regions of interest.
Cross-sectional analyses evaluated the colocalization and association of microglia density with other biomarkers, and mediation pathways were examined.

Main Results:

Higher microglia density colocalized more frequently with tau pathology (10 regions) than with amyloid (8 regions) or neurodegeneration (4 regions) in cognitively impaired individuals.
Microglia density was positively associated with tau and negatively associated with neurodegeneration in specific brain regions.
Microglia density mediated tau-associated neurodegeneration, and in amyloid-positive individuals, it also mediated amyloid-associated tau and tau spreading.

Conclusions:

Microglia activation is closely linked to tau pathology in Alzheimer's disease.
Targeting glia, particularly microglia, presents a promising therapeutic avenue for intervening in tau-associated neurodegeneration, even in the absence of amyloid pathology.