Related Experiment Video
Updated: Jul 13, 2026
Measurement of Extracellular Ion Fluxes Using the Ion-selective Self-referencing Microelectrode Technique
Published on: May 3, 2015
In-vivo measurement of activated microglia in dementia
A Cagnin1, D J Brooks, A M Kennedy
1MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK.
Background:
Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease.
Methods:
We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site.
Findings:
In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex.
Interpretation:
In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.
Insights
Microglial activation, indicated by increased peripheral benzodiazepine binding sites, is detected in Alzheimer's disease patients. This brain imaging finding suggests microglial activation is an early event in Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Microglia play a crucial role in the brain's immune response to neurodegeneration.
- Activated microglia show increased expression of peripheral benzodiazepine binding sites.
- These sites are abundant on mononuclear phagocyte lineage cells.
Purpose of the Study:
- To investigate peripheral benzodiazepine binding site expression in healthy individuals and Alzheimer's disease patients using brain imaging.
- To assess glial activation in vivo.
Main Methods:
- Positron emission tomography (PET) scans were performed on 15 healthy individuals and 9 patients (8 with Alzheimer's disease, 1 with mild cognitive impairment).
- Quantitative in-vivo measurements of glial activation utilized carbon-11-labelled (R)-PK11195, a specific ligand for peripheral benzodiazepine binding sites.
Main Results:
- No significant age-related change in [11C](R)-PK11195 binding was observed in healthy individuals, except for an age-dependent increase in the thalamus.
- Alzheimer's disease patients exhibited significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex.
Conclusions:
- In-vivo detection of elevated [11C](R)-PK11195 binding in Alzheimer-type dementia indicates microglial activation.
- This suggests microglial activation is an early event in the pathogenesis of Alzheimer's disease, even in mild and early forms.
