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In vivo detection of microglial activation in frontotemporal dementia
Open accessAbstract
Using positron emission tomography and [(11)C](R)-PK11195, a marker of "peripheral benzodiazepine sites" that is upregulated on activated microglia during progressive tissue pathology, we show increased binding of [(11)C](R)-PK11195 in frontotemporal lobar degeneration in the typically affected frontotemporal brain regions. This implies the presence of an active glial response reflecting progressive neuronal degeneration. It also suggests that increased [(11)C](R)-PK11195 binding, previously demonstrated for Alzheimer's disease, may occur independently from increased amyloid plaque formation, given that it is not a characteristic feature of frontotemporal lobar degeneration.
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“In vivo PET studies320,321 and immunohistochemistry studies322–324 have found increased microglial activation in the frontal and temporal cortices of patients with FTD.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [320]
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BackgroundInnate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437
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Guzman-Martinez, L., Maccioni, R. B., Andrade, V., Navarrete, L. P., Pastor, M. G., & Ramos-Escobar, N. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01008 · Cited by 702
“In this way, the neuroinflammatory process has been proposed as possible diagnostic tools, through in vivo uptake of the microglia, using positron emission tomography (PET) images with the translocator protein (TSPO) ligand [11C]-PK11195 in the FTD and other tauopathies (Cagnin et al., 2004; Venneti et al., 2009; Zhan…”
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“…neurotoxicantinduced injury, TSPO has been used as a biomarker of brain injury and inflammation in neurodegenerative diseases (Cagnin et al., 2001a; Cagnin et al., 2004; Gerhard et al., 2003; Gerhard et al., 2004; Gerhard et al., 2006; Messmer and Reynolds, 1998; Ouchi et al., 2005; Pavese et al.,…”
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Inflammation in ALS/FTD pathogenesis
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Neuroinflammation in frontotemporal dementia
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“In patients with frontotemporal dementia, PET showed [11C](R)PK11195 binding in the frontal, medial temporal, and subcortical regions (Cagnin et al, 2004).”
BackgroundNeuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease
Farfara, D., Lifshitz, V., & Frenkel, D. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00314.x · Cited by 216
“Furthermore, studies found activated microglia in vivo (in the brains of AD patients), by using positron emission tomography and 11C-PK111995, which is a marker of peripheral benzodiazepine binding sites that are upregulated on the activated microglia [49, 50].”
BackgroundPositron emission tomography imaging in dementia
HERHOLZ, K., CARTER, S. F., & JONES, M. (2007) · The British Journal of Radiology · doi:10.1259/bjr/97295129 · Cited by 287
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BackgroundSelf-citationRecent developments on PET radiotracers for TSPO and their applications in neuroimaging
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“…amyotrophic lateral sclerosis (Turner et al. 2004), corticobasal degeneration (Gerhard et al. 2004; Henkel et al. 2004), frontotemporal dementia (Cagnin et al. 2004), Parkinson’s disease (Ouchi et al. 2005; Gerhard et al. 2006), upper motor neuron syndromes (Turner et al. 2005), HIV infection…”
BackgroundInnate immune activation in neurodegenerative diseases
Castro‐Gomez, S., & Heneka, M. T. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.010 · Cited by 176
A TSPO ligand is protective in a mouse model of multiple sclerosis
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“…2007) traumatic brain injury, (Papadopoulos & Lecanu, 2009) ischaemic stroke, (Cosenza-Nashat, 2009; Gerhard, 2005) frontotemporal dementia, (Cagnin, 2004) amyotrophic lateral sclerosis, (Turner, 2004) Parkinson’s (Ouchi, 2005) and multiple sclerosis (MS) (Versijpt, 2005; Vowinckel, 1997).”
A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis
Nutma, E., Stephenson, J. A., Gorter, R. P., de Bruin, J., Boucherie, D. M., Donat, C. K., Breur, M., van der Valk, P., Matthews, P. M., Owen, D. R., et al. (2019) · Brain · doi:10.1093/brain/awz287 · Cited by 138
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“It is thus not surprising that increased [(11)C](R)-PK11195 binding is also found in non-amyloid-related degenerative dementia, such as frontotemporal lobar degeneration, a disease characterized by intracellular tau-positive or ubiquitin-positive inclusions and neuronal degeneration.(58) In frontotemporal lobar degene…”
Self-citationThe Role of Neuroinflammation in Dementias
Pasqualetti, G., Brooks, D. J., & Edison, P. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0531-7 · Cited by 133
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“Although [C]-(R)-PK11195 has already been used to image activated microglia cells in, among others, stroke [5–8], multiple sclerosis [9–12], herpes encephalitis [13], Parkinson’s disease [14, 15], and Alzheimer’s disease [16–18], it is not an ideal tracer, since it shows low brain uptake and high nonspecific binding.”
MethodMolecular Imaging of Inflammation/Infection: Nuclear Medicine and Optical Imaging Agents and Methods
Signore, A., Mather, S. J., Piaggio, G., Malviya, G., & Dierckx, R. A. (2010) · Chemical Reviews · doi:10.1021/cr900351r · Cited by 129
Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum
Bevan-Jones, W. R., Cope, T. E., Jones, P. S., Kaalund, S. S., Passamonti, L., Allinson, K., Green, O., Hong, Y. T., Fryer, T. D., Arnold, R., et al. (2020) · Brain · doi:10.1093/brain/awaa033 · Cited by 124
“In vivo PET studies in small samples have shown that neuroinflammation anticipates atrophy in clinically established FTD (Cagnin et al., 2004) and precedes both symptoms and the detectability of tau aggregation by PET in MAPT mutation carriers (Miyoshi et al.”
BackgroundVenneti, S., Wang, G., Nguyen, J., & Wiley, C. A. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318188b204 · Cited by 122
“The extent of microglial activation and of reactive astrocytosis was assessed in postmortem brain tissues from patients with cerebrovascular infarcts, MS, FTD, ALS, and AD (n = 10 each condition) and compared with controls (n = 6).”
InfluentialImaging of microglia in patients with neurodegenerative disorders
Politis, M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00096 · Cited by 111
Translocator Protein 18 kDa Negatively Regulates Inflammation in Microglia
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“…up-regulated in neurological disorders including AD (Papadopoulos et al. 2006; Edison et al. 2008; Yasuno et al. 2008), fronto-temporal dementia (Cagnin et al. 2004), multiple sclerosis (Vowinckel et al. 1997; Versijpt et al. 2005), Huntington's disease (Pavese et al. 2006), amyotrophic lateral…”
BackgroundPatterns of microglial cell activation in frontotemporal lobar degeneration
Lant, S. B., Robinson, A. C., Thompson, J. C., Rollinson, S., Pickering‐Brown, S., Snowden, J. S., Davidson, Y. S., Gerhard, A., & Mann, D. M. A. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12092 · Cited by 102
“have also been successful in showing the presence of microglial activation in vivo in progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD) [24,25], and also in a small cohort of FTLD patients [26].”
BackgroundImaging of neuroinflammation in dementia: a review
Stefaniak, J. D., & O'Brien, J. T. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2015-311336 · Cited by 113
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“…powerful imaging tool for AD-associated neuroinflammation (Airas et al., 2018; Nothdurfter et al., 2012; Ger-hard et al., 2000; Ramsay et al., 1992; Cagnin et al., 2004; Chen and Guilarte, 2008; Papadopoulos and Lecanu, 2009), which has also been validated in the brains of individuals with AD…”
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“…Computed Tomography (SPECT) or Magnetic Resonance Imaging (MRI) in patients targeting activated microglial receptors or astrocytic metabolites have shown gliosis throughout various symptomatic stages of ALS and FTD while absent in non-disease controls (Cagnin et al., 2004; Chiò et al., 2014).”
Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease
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“Microglial activation can play a role in other neurodegenerative diseases such as dementia with Lewy bodies, frontotemporal dementia and Parkinson’s disease (Cagnin et al., 2004; Surendranathan et al., 2015).”
BackgroundInnate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases
Novellino, F., Saccà, V., Donato, A., Zaffino, P., Spadea, M. F., Vismara, M. F. M., Arcidiacono, B., Malara, N., Presta, I., & Donato, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031115 · Cited by 107
“In vivo PET imaging with the PK11195 ligand, which identifies inflammatory glia, has revealed the presence of activated microglia in the frontotemporal lobes of patients with FTD, and this finding was evident before the atrophy occurred [156].”
BackgroundThe Translocator Protein (18 kDa): Central Nervous System Disease and Drug Design
Scarf, A. M., Ittner, L. M., & Kassiou, M. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm8011678 · Cited by 98
PET/CT in diagnosis of dementia
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Evaluation of Reference Tissue Models for the Analysis of [ 11 C]( R )-PK11195 Studies
Kropholler, M. A., Boellaard, R., Schuitemaker, A., Folkersma, H., van Berckel, B. N. M., & Lammertsma, A. A. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600289 · Cited by 94
“…2003; Versijpt et al, 2005) and various other diseases (Pappata et al, 1991; Banati et al, 1999, 2001; Goerres et al, 2001; Cagnin et al, 2001b, 2004; Cicchetti et al, 2002; Gerhard et al, 2003, 2004, 2005b; Turner et al, 2004, 2005; Venneti et al, 2004; Henkel et al, 2004; Ouchi et al, 2005).”
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“disorders, inflammatory mechanisms might participate in the pathophysiology of FTLD, since the disease is characterized by in vivo activation of microglia [11], and increased levels of intrathecal pro-inflammatory mediators [12,13].”
BackgroundFrontal Cortex Neuropathology in Dementia Pugilistica
Saing, T., Dick, M. B., Nelson, P. T., Kim, R. C., Cribbs, D. H., & Head, E. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1957 · Cited by 92
“Similar microglial activation has been described in FTLD, both by in vivo imaging (Cagnin et al., 2004), and by immunohistochemistry (Arnold et al.”
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“…et al., 2006; Bartels et al., 2010), Huntington’s disease (Pavese et al., 2006; Tai et al., 2007; Politis et al., 2008, 2011), Multiple Sclerosis (Banati et al., 2000; Debruyne et al., 2003; Versijpt et al., 2005) and AD (Cagnin et al., 2001, 2004; Edison et al., 2008; Yokokura et al., 2011).”
BackgroundBoxer, A. L., Gold, M., Huey, E. D., Gao, F., Burton, E. A., Chow, T. W., Kao, A. W., Leavitt, B. R., Lamb, B. T., Grether, M. E., et al. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.03.002 · Cited by 84
A predictive coding framework of allostatic–interoceptive overload in frontotemporal dementia
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Widespread and Prolonged Increase in (R)-11C-PK11195 Binding After Traumatic Brain Injury
Folkersma, H., Boellaard, R., Yaqub, M. M., Kloet, R. W., Windhorst, A. D., Lammertsma, A. A., Vandertop, W. P., & van Berckel, B. N. M. (2011) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.084061 · Cited by 76
“It has been suggested that microglial activation may play an important role in a variety of neuroinflammatory and neurodegenerative diseases (7,8).”
BackgroundMiyoshi, M., Shinotoh, H., Wszolek, Z. K., Strongosky, A. J., Shimada, H., Arakawa, R., Higuchi, M., Ikoma, Y., Yasuno, F., Fukushi, K., et al. (2010) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2010.04.004 · Cited by 75
“A PBR ligand, [11C](R)-PK11195, has been widely used for PET analyses as a marker of activated microglia in brain diseases including frontotemporal dementia and presymptomatic Huntington’s disease gene carriers [8,23,24].”
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“[87] reported a distribution pattern of microglia activation mirroring the pattern of neuronal metabolic dysfunction and clinical impairment in five patients fulfilling Neary criteria for FTD [90].”
BackgroundExploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD
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In vivo evidence for microglial activation in neurodegenerative dementia
Cagnin, A., Kassiou, M., Meikle, S. R., & Banati, R. B. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2006.00694.x · Cited by 71
“Patients underwent [(11)C](R)PK11195 PET and a volumetric T1-weighted MR brain scan as previously described (33).”
MethodSelf-citationSuridjan, 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
In vivo PET imaging of neuroinflammation in Alzheimer’s disease
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“…in frontotemporal lobar degeneration in the frontotemporal brain regions, suggesting that microglial activation may occur independently from increased amyloid plaque formation (Cagnin et al. 2004), and could also be an intrinsic process in other pathways, such as tau pathology (Zhang 2015).”
BackgroundChen, M., & Guilarte, T. R. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfj172 · Cited by 70
“Increased PBR levels have been described in models of chemical-induced neurotoxicity (Chen et al., 2004; Guilarte et al., 1995; Kuhlmann and Guilarte, 1997, 1999, 2000), ischemic stroke (Gerhard et al., 2000, 2005; Pappata et al., 2000; Stephenson et al., 1995), physical trauma (Miyazawa et al., 1995; Raghavendra Rao…”
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“It can be made visible in vivo by positron emission tomography in the brains of adults with multiple sclerosis (8), dementia (9) and Parkinson’s disease (10).”
BackgroundVicidomini, C., Panico, M., Greco, A., Gargiulo, S., Coda, A. R. D., Zannetti, A., Gramanzini, M., Roviello, G. N., Quarantelli, M., Alfano, B., et al. (2014) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2014.11.009 · Cited by 70
“Up-regulation of TSPO is present in many CNS diseases, including Alzheimer’s [40], Huntington’s [41,42], Parkinson’s [43], amyotrophic lateral sclerosis [44], frontotemporal dementia [45] multiple sclerosis [46,47], brain trauma [7], and stroke [48,49] as well as in both CNS and non-CNS tumors [50,51], and in atherosc…”
BackgroundAn update on human astrocytes and their role in development and disease
de Majo, M., Koontz, M., Rowitch, D. H., & Ullian, E. M. (2020) · Glia · doi:10.1002/glia.23771 · Cited by 69
A synergetic turn in cognitive neuroscience of brain diseases
Ibanez, A., Kringelbach, M. L., & Deco, G. (2024) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2023.12.006 · Cited by 65
Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia
Mishra, A., Ferrari, R., Heutink, P., Hardy, J., Pijnenburg, Y. A. L., & Posthuma, D. (2017) · Brain · doi:10.1093/brain/awx066 · Cited by 64
Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia
Kadir, A., & Nordberg, A. K. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.077164 · Cited by 64
“Elevated levels of 11C-(R)-PK11195 have been observed in brains of patients with FTD (163) and Huntington disease (164).”
BackgroundMa, L., Zhang, H., Liu, N., Wang, P., Guo, W.-Z., Fu, Q., Jiao, L.-B., Ma, Y., & Mi, W. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.02.001 · Cited by 66
Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging
Zhang, J. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0236-5 · Cited by 62
“Molecular PET imaging with [(11)C]-PK11195 has found that compared with controls, the mean [(11)C]-PK11195 binding was significantly increased in patients with FTD (n = 5, including four patients with progressive non-fluent aphasia and one patient with behavioral variant FTD) in regions such as the left dorsolateral p…”
MethodBehavioral and transcriptomic analysis of Trem2-null mice: not all knockout mice are created equal
Kang, S. S., Kurti, A., Baker, K. E., Liu, C.-C., Colonna, M., Ulrich, J. D., Holtzman, D. M., Bu, G., & Fryer, J. D. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddx366 · Cited by 62
Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration
Woollacott, I., Toomey, C. E., Strand, C., Courtney, R. J., Benson, B. C., Rohrer, J. D., & Lashley, T. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01907-0 · Cited by 65
Giovannini, M. G., Lana, D., Traini, C., & Vannucchi, M. G. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112358 · Cited by 64
“The dysfunction of microglia has been described in many CNS disorders, such as AD [133], frontotemporal dementia [134,135] and PD [136].”
BackgroundMicroglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia
Malpetti, M., Cope, T., Street, D., Jones, P. S., Hezemans, F. H., Mak, E., Tsvetanov, K. A., Rittman, T., Bevan-Jones, W. R., Patterson, K. E., et al. (2023) · Brain · doi:10.1093/brain/awad078 · Cited by 63
Scott, L. L., & Downing, T. G. (2017) · Toxins · doi:10.3390/toxins10010022 · Cited by 59
“Whether microglia are neuroprotective in the AD brain or facilitate and contribute to the neurotoxicity is currently still under active investigation, but several studies [120,121] have shown that the cognitive decline in AD is significantly correlated to the number of activated microglia rather than amyloid depositio…”
BackgroundZou, J., Tao, S., Johnson, A. S., Tomljanovic, Z., Polly, K., Klein, J., Razlighi, Q. R., Brickman, A. M., Lee, S., Stern, Y., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.019 · Cited by 55
“However, neuroinflammation may be a nonspecific response to neurodegeneration, as TSPO binding is increased in several non-Alzheimer neurodegenerative disorders, including frontotemporal dementia, Parkinson's disease, and amyotrophic lateral sclerosis (Cagnin et al., 2004; Corcia et al., 2012; Gerhard et al., 2006), a…”
BackgroundKropholler, M. A., Boellaard, R., van Berckel, B. N. M., Schuitemaker, A., Kloet, R. W., Lubberink, M., Jonker, C., Scheltens, P., & Lammertsma, A. A. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600488 · Cited by 56
11 C‐PK11195 PET–based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis
Tondo, G., Iaccarino, L., Cerami, C., Vanoli, G. E., Presotto, L., Masiello, V., Coliva, A., Salvi, F., Bartolomei, I., Mosca, L., et al. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51112 · Cited by 56
Nerella, S. G., Bhattacharya, A., Joshi, R. K., Nagaraj, C., Bharath, R. D., & Kumar, P. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01053 · Cited by 59
Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology
Hartnell, I. J., Woodhouse, D., Jasper, W., Mason, L., Marwaha, P. K., Graffeuil, M., Lau, L. C., Norman, J. L., Chatelet, D. S., Buée, L., et al. (2023) · Brain · doi:10.1093/brain/awad309 · Cited by 56
“However, some studies have shown increased 11 C-PK11195 binding in subcortical regions of clinically diagnosed PSP patients 55 as well as in the frontal lobe.”
ResultSystems biology of neurodegenerative diseases
Wood, L. B., Winslow, A. R., & Strasser, S. D. (2015) · Integrative Biology · doi:10.1039/c5ib00031a · Cited by 56
Glial biomarkers in human central nervous system disease
Garden, G. A., & Campbell, B. M. (2016) · Glia · doi:10.1002/glia.22998 · Cited by 59
“Activated microglial receptors or astrocytic metabolites have been observed throughout the course of ALS and in fact demonstrate a relationship between gliosis and disease progression (Cagnin et al., 2004; Chio et al., 2014).”
BackgroundThe emerging role of PET imaging in dementia
Iaccarino, L., Sala, A., Caminiti, S. P., & Perani, D. (2017) · F1000Research · doi:10.12688/f1000research.11603.1 · Cited by 52
“It should be taken into account that the characteristics of 18 F-FDG-PET hypometabolic patterns in MCI individuals can indicate the prognostic risk of progression to different dementia conditions (see above) 23–25 , In patients with dementia, amyloid PET is recognized as a powerful tool to differentiate conditions cha…”
MethodAssogna, M., Casula, E. P., Borghi, I., Bonnì, S., Samà, D., Motta, C., Lorenzo, F. D., D’Acunto, A., Porrazzini, F., Minei, M., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200426 · Cited by 51
“Further in vivo imaging studies using molecular ligands for microglial activity such as TSPO-ligands 11C-PK11195 [10, 11] could help to further deepen these complex interactions.”
Chauveau, F., Becker, G., & Boutin, H. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05425-w · Cited by 54
Inflammation and clinical presentation in neurodegenerative disease: a volatile relationship
Bettcher, B. M., & Kramer, J. H. (2012) · Neurocase · doi:10.1080/13554794.2011.654227 · Cited by 49
Dementia spectrum disorders: lessons learnt from decades with PET research
Wilson, H., Pagano, G., & Politis, M. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-01975-4 · Cited by 50
Banati, R. B., & Hickie, I. B. (2009) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2009.tb02371.x · Cited by 46
Self-citationBlood inflammation relates to neuroinflammation and survival in frontotemporal lobar degeneration
Malpetti, M., Swann, P., Tsvetanov, K. A., Chouliaras, L., Strauss, A., Chikaura, T., Murley, A. G., Ashton, N. J., Barker, P. B., Jones, P. S., et al. (2024) · Brain · doi:10.1093/brain/awae269 · Cited by 48
Plasma levels of progranulin and interleukin-6 in frontotemporal lobar degeneration
Gibbons, L., Rollinson, S. J., Thompson, J. C., Robinson, A., Davidson, Y. S., Richardson, A. M. T., Neary, D., Pickering-Brown, S. M., Snowden, J. S., & Mann, D. M. A. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.10.023 · Cited by 44
“, 2012), perhaps reflecting increased microglial activity especially in GRN carriers (Ahmed et al., 2007; Cagnin et al., 2004) or in normal control subjects.”
Apolipoprotein E polymorphisms in frontotemporal lobar degeneration: A meta‐analysis
Rubino, E., Vacca, A., Govone, F., Martino, P. D., Pinessi, L., & Rainero, I. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.10.013 · Cited by 44
“In patients with FTLD, neuroimaging and genetic studies suggested that an enhanced inflammatory response might be involved in disease risk and progression [46,47].”
In vivo PET imaging of neuroinflammation in familial frontotemporal dementia
Malpetti, M., Rittman, T., Jones, P. S., Cope, T. E., Passamonti, L., Bevan-Jones, W. R., Patterson, K., Fryer, T. D., Hong, Y. T., Aigbirhio, F. I., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323698 · Cited by 43
Neuroimmune Tau Mechanisms: Their Role in the Progression of Neuronal Degeneration
Cortés, N., Andrade, V., Guzmán‐Martínez, L., Estrella, M., & Maccioni, R. B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040956 · Cited by 43
Glial cells and adaptive immunity in frontotemporal dementia with tau pathology
Hartnell, I. J., Blum, D. L., Nicoll, J. A. R., Dorothée, G., & Boche, D. (2020) · Brain · doi:10.1093/brain/awaa457 · Cited by 41
Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative Proteinopathies
Kohl, Z., Schlachetzki, J. C. M., Stemick, J., Hornauer, P., Münch, M., Adame, A., Riemenschneider, M. J., Winkler, J., & Masliah, E. (2017) · Neural Plasticity · doi:10.1155/2017/3851262 · Cited by 39
“In FTLD, findings about neuroinflammatory processes are still very limited: A pilot PET imaging study using the [(11)C](R)-PK11195 ligand identified microglia activation in frontotemporal brain regions of FTLD patients [53].”
Boström, G., Freyhult, E., Virhammar, J., Alcolea, D. A., Tumani, H., Otto, M., Brundin, R., Kilander, L., Löwenmark, M., Giedraitis, V., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201565 · Cited by 43
“Similar to cellular changes in the AD brain, microgliosis and astrocytosis are typically seen also in the FTD brain [13].”
Luus, C., Hanani, R., Reynolds, A. J., & Kassiou, M. (2010) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.1752 · Cited by 38
Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia
Kreisl, W. C., Henter, I. D., & Innis, R. B. (2017) · Advances in pharmacology · doi:10.1016/bs.apha.2017.08.004 · Cited by 41
Chu, M., Wen, L., Jiang, D., Liu, L., Nan, H., Yue, A., Wang, Y., Wang, Y., Qu, M., Wang, N., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02746-5 · Cited by 33
“Study in FTD using the TSPO ligand 11C-PK1119 was reported, which labelled the presence of an active glial response in frontotemporal brain regions, providing evidence for neuroinflammation in diseasespecific brain regions[43].”
MethodPatterns of Microglial Cell Activation in Alzheimer Disease and Frontotemporal Lobar Degeneration
Taipa, R., Brochado, P., Robinson, A., Reis, I., Costa, P., Mann, D. M., Melo Pires, M., & Sousa, N. (2017) · Neurodegenerative Diseases · doi:10.1159/000457127 · Cited by 37
Azrad, M., Zeineh, N., Weizman, A., Veenman, L., & Gavish, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030594 · Cited by 37
Metadata
- Authors
- Cagnin, A., Rossor, M., Sampson, E. L., MacKinnon, T., & Banati, R. B.
- Affiliations
- University of Padua (IT)
- National Hospital for Neurology and Neurosurgery (GB)
- Hammersmith Hospital (GB)
- The University of Sydney (AU)
- Corresponding author
- Banati, Richard B.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2004-11-23
- Volume
- 56
- Issue
- 6
- Pages
- 894-897
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2067897311
- Cited by
- 187
- References
- 10
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 14 · 2022: 7 · 2021: 11 · 2020: 22 · 2019: 13 · 2018: 7 · 2017: 16 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 7 · 2012: 7
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- microglial activation, frontotemporal lobar degeneration, frontotemporal dementia, [11C]PK11195, translocator protein (TSPO), positron emission tomography, glial response, neurodegeneration, amyloid plaques
- MeSH terms
- Aged, Dementia, Follow-Up Studies, Humans, Isoquinolines, Middle Aged, Protein Binding, Chi-Square Distribution, Microglia
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