In-vivo measurement of activated microglia in dementia
Abstract
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.
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11C-PK11195 (PK-PET) binds to the 18-kDA translocator protein (TSPO), a mitochondrial membrane protein upregulated in activated microglia.
“One of the earliest and the most widely used PET markers of neuroinflammation in neurodegenerative studies is 11C -PK11195 (PK-PET) which binds to the 18-kDA translocator protein (TSPO), a mitochondrial membrane protein that is upregulated in activated microglia [215].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [215]
PK-PET is increased in entorhinal, temporal, parietal, and cingulate cortex in AD, in frontotemporal regions in FTD, while PSP shows increased PK-PET binding in thalamus, putamen, and pallidum, showing differential distribution of neuroinflammatory processes in different types of dementia.
“PK-PET is increased in the entorhinal, temporal, parietal and cingulate cortex in AD, in the frontotemporal regions in FTD, while PSP shows increased PK-PET binding in the thalamus, putamen and pallidum, showing differential distribution of neuroinflammatory processes in different types of dementia [215–218].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [215]
AD patients show significantly increased regional TSPO ligand binding in the cortices compared to controls using TSPO-specific radiotracers.
“AD patients all showed significantly increased regional TSPO ligand binding in the cortices compared to controls.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [135]
The increase in Aβ deposition induces the activation of astrocytes as well as microglia.
“The increase in Aβ deposition induces the activation of astrocytes as well as microglia (Cagnin et al., 2001).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Cagnin et al., 2001
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- Authors
- Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., Jones, T., & Banati, R. B.
- Affiliations
- Hammersmith Hospital (GB)
- Corresponding author
- Banati, Richard B
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 358
- Issue
- 9280
- Pages
- 461-467
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2149954869
- Cited by
- 1,054
- References
- 5
- Citations by year
- 2026: 6 · 2025: 35 · 2024: 30 · 2023: 32 · 2022: 35 · 2021: 48 · 2020: 39 · 2019: 51 · 2018: 38 · 2017: 42 · 2016: 52 · 2015: 52 · 2014: 60 · 2013: 49 · 2012: 57
- FWCI
- 22.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- microglial activation, Alzheimer's disease, [11C](R)-PK11195, positron emission tomography, dementia, brain aging, thalamus, entorhinal cortex, cingulate cortex, temporoparietal cortex, neuroinflammation, early disease detection
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Carbon Radioisotopes, Female, Humans, Inflammation, Isoquinolines, Magnetic Resonance Imaging, Male, Middle Aged, Receptors, GABA-A, Tomography, Emission-Computed, Case-Control Studies, Microglia
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