Related Experiment Video
Updated: Jul 7, 2026
07:18
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.
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.
Related Concept Videos
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:26Alzheimer's Disease: Overview
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
01:22Dementia l: Introduction
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...