The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
Citations
Cites
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
The processing-speed theory of adult age differences in cognition
Salthouse, T. A. (1996) · Psychological Review · doi:10.1037/0033-295x.103.3.403 · Cited by 5,902
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287
HULETTE, C. M., WELSH-BOHMER, K. A., MURRAY, M. G., SAUNDERS, A. M., MASH, D. C., & MCINTYRE, L. M. (1998) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199812000-00009 · Cited by 311
NSAIDs and incident Alzheimer’s disease. The Rotterdam study
In ’t Veld, B. A., Launer, L. J., Hoes, A. W., Ott, A., Hofman, A., Breteler, M. M. B., & Stricker, B. H. C. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00096-7 · Cited by 145
Research works printed but not linked: 22
- Kreutzberg, 1996, Microglia: a sensor for pathological events in the CNS, Trends Neurosci, 19, 312, 10.1016/0166-2236(96)10049-7 · DOI · Paper page
- Alzheimer, 1911, Über eigenartige Krankheitsfälle des späteren Alters. Z. ges, Neurol Psych, 4, 356, 10.1007/BF02866241 · DOI
- Barger, 1997, Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E, Nature, 388, 878, 10.1038/42257 · DOI · Paper page
- Tan, 1999, Microglial activation resulting from CD40-CD40L interaction after beta-amyloid, Science, 286, 2352, 10.1126/science.286.5448.2352 · DOI
- Banati, 1997, PK (‘peripheral benzodiazepine’)-binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia, J Neurocytol, 26, 77, 10.1023/A:1018567510105 · DOI
- Conway, 1998, Temporal changes in glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding in relation to imidazoline-I2-receptor and alpha 2-adrenoreceptor binding in the hippocampus following transient global forebrain ischaemia in the rat, Neuroscience, 82, 805, 10.1016/S0306-4522(97)00321-7 · DOI
- Sette, 1993, In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anaesthetised baboon, Stroke, 24, 2046, 10.1161/01.STR.24.12.2046 · DOI
- Banati, 2000, The peripheral benzodiazepine binding sites in the brain in multiple sclerosis: quantitative in vivo-imaging of microglia as a measure of disease activity, Brain, 123, 2321, 10.1093/brain/123.11.2321 · DOI · Paper page
- Lammertsma, 1996, Simplified reference tissue model for PET receptor studies, Neuroimage, 4, 153, 10.1006/nimg.1996.0066 · DOI
- Niemann, 2000, Evidence of a smaller left hippocampus and left temporal horn in both patients with first episode schizophrenia and normal control subjects, Psychiatry Res Neuroimaging, 99, 93, 10.1016/S0925-4927(00)00059-7 · DOI
- Hu, 2000, Cortical dysfunction in non-demented Parkinson's disease patients: a combined 31P-MRS and 18FDG-PET study, Brain, 123, 340, 10.1093/brain/123.2.340 · DOI
- Cunningham, 1993, Spectral analysis of dynamic PET studies, Cereb Blood Flow Metab, 13, 15, 10.1038/jcbfm.1993.5 · DOI
- Hajnal, 1995, Detection of subtle brain changes using subvoxel registration and subtraction of serial MR images, J Comput Assist Tomogr, 19, 677, 10.1097/00004728-199509000-00001 · DOI
- Dumont, 1999, In vivo evaluation in mice and metabolism in blood of human volunteers of [123I]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation, Eur J Nucl Med, 26, 194, 10.1007/s002590050376 · DOI
- Myers, 1991, (3H) PK 11195 and the localisation of secondary thalamic lesions following focal ischemia in rat motor cortex, Neurosci Lett, 133, 20, 10.1016/0304-3940(91)90047-W · DOI
- Blinzinger, 1968, Displacement of synaptic terminals from regenerating motoneurons by microglial cells, Z Zellforsch Mikrosk Anat, 85, 145, 10.1007/BF00325030 · DOI
- Groom, 1995, PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease, J Nucl Med, 36, 2207
- Shah, 1994, Synthesis of the enantiomer of [N-methyl-11C]PK11195 and comparison of their behaviours as PK (peripheral benzodiazepine) binding site radioligands in rats, Nucl Med Biol, 21, 573, 10.1016/0969-8051(94)90022-1 · DOI
- Killiany, 2000, Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease, Ann Neurol, 47, 430, 10.1002/1531-8249(200004)47:4<430::AID-ANA5>3.0.CO;2-I · DOI
- Minoshima, 1997, Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease, Ann Neurol, 42, 85, 10.1002/ana.410420114 · DOI · Paper page
- Meguro, 1999, Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and cortices in the non-human primate as shown by PET: implications for Alzheimer's disease, Brain, 122, 1519, 10.1093/brain/122.8.1519 · DOI
- Price, 1999, Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease, Ann Neurol, 45, 358, 10.1002/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X · DOI
Cited by
Sorted by citations
Items 101–110 of 110
Suridjan, I., Rusjan, P. M., Voineskos, A. N., Selvanathan, T., Setiawan, E., Strafella, A. P., Wilson, A. A., Meyer, J. H., Houle, S., & Mizrahi, R. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.09.021 · Cited by 71
Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Walker, D., & Lue, L.-F. (2007) · Current Neuropharmacology · doi:10.2174/157015907782793667 · Cited by 66
Microglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60
Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study
Parbo, P., Ismail, R., Sommerauer, M., Stokholm, M. G., Hansen, A. K., Hansen, K. V., Amidi, A., Schaldemose, J. L., Gottrup, H., Brændgaard, H., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.06.004 · Cited by 63
Self-citationIn vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease
Terada, T., Yokokura, M., Obi, T., Bunai, T., Yoshikawa, E., Ando, I., Shimada, H., Suhara, T., Higuchi, M., & Ouchi, Y. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09400-2 · Cited by 60
Prospects and challenges of imaging neuroinflammation beyond TSPO in Alzheimer’s disease
Faculty, O. B. O. T. M., Boche, D., Gerhard, A., & Rodriguez-Vieitez, E. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04462-w · Cited by 55
Hoozemans, J. J., van Haastert, E. S., Veerhuis, R., Arendt, T., Scheper, W., Eikelenboom, P., & Rozemuller, A. J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-27 · Cited by 52
Streptozotocin-induced astrocyte mitochondrial dysfunction is ameliorated by FTO inhibitor MO-I-500
Cockova, Z., Honc, O., Telensky, P., Olsen, M. J., & Novotny, J. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00063 · Cited by 34
Alzheimer's disease biomarkers: correspondence between human studies and animal models
Sabbagh, J. J., Kinney, J. W., & Cummings, J. L. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.04.010 · Cited by 27
Vicente-Rodríguez, M., Mancuso, R., Peris-Yague, A., Simmons, C., NIMA Consortium, Wlazly, D., Dickinson, A., Foster, A., Knight, C., Leckey, C., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02769-y · Cited by 17
“Accordingly, using PET imaging, increased TSPO signal has been observed in a range of human neurodegenerative diseases with an inflammatory component, such as simian immunodeficiency virus encephalitis [10], multiple sclerosis [11], Huntington’s [12] and Alzheimer’s disease [13].”
BackgroundSelf-citation
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
