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.
Integrity signals
Registry
Cites
Statistics
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 vivo PET and immunohistochemistry studies found increased microglial activation in the frontal and temporal cortices of patients with FTD.
“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]
Cites
Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047 · see citing works
In-vivo measurement of activated microglia in dementia
Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., Jones, T., & Banati, R. B. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05625-2 · Cited by 1,054 · see citing works
Self-citationThe peripheral benzodiazepine binding site in the brain in multiple sclerosis
Banati, R. B., Newcombe, J., Gunn, R. N., Cagnin, A., Turkheimer, F., Heppner, F., Price, G., Wegner, F., Giovannoni, G., Miller, D. H., et al. (2000) · Brain · doi:10.1093/brain/123.11.2321 · Cited by 661 · see citing works
Self-citationBruyn, R. P. M. (2003) · Clinical Neurology and Neurosurgery · doi:10.1016/s0303-8467(02)00110-5 · Cited by 510 · see citing works
Thalamic microglial activation in ischemic stroke detected in vivo by PET and [ 11 C]PK11195
Pappatà, S., Levasseur, M., Gunn, R. N., Myers, R., Crouzel, C., Syrota, A., Jones, T., Kreutzberg, G. W., & Banati, R. B. (2000) · Neurology · doi:10.1212/wnl.55.7.1052 · Cited by 252 · see citing works
Self-citationMyers, R., Manjil, L. G., Cullen, B. M., Price, G. W., Frackowiak, R. S. J., & Cremer, J. E. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.64 · Cited by 182 · see citing works
Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD
Rosen, H., Hartikainen, K. M., Jagust, W., Kramer, J. H., Reed, B., Cummings, J. L., Boone, K., Ellis, W. G., Miller, C. A., & Miller, B. L. (2002) · Neurology · doi:10.1212/wnl.58.11.1608 · Cited by 175 · see citing works
The neuropathology and biochemistry of frontotemporal dementia
Muñoz, D. G., Dickson, D. W., Bergeron, C., Mackenzie, I. R., Delacourte, A., & Zhukareva, V. A. (2003) · Annals of Neurology · doi:10.1002/ana.10571 · Cited by 83 · see citing works
Microglial reaction in Pick's disease
Paulus, W., Bancher, C., & Jellinger, K. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90147-d · Cited by 42 · see citing works
Pick body disease and Pick syndrome*
Uchihara, T., Ikeda, K., & Tsuchiya, K. (2003) · Neuropathology · doi:10.1046/j.1440-1789.2003.00523.x · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
“…in TBK1 are associated with developing FTD, 317,318 and variants in TREM2 increase an individual ’ s risk of developing FTD. 319 In vivo PET studies 320,321 and immunohistochemistry studies 322 – 324 have found increased microglial activation in the frontal and temporal cortices of patients with…”
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 · see citing works
Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., Groyer, G., Adams, D., & Schumacher, M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3295 · Cited by 930 · see citing works
Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response
Bachiller, S., Jiménez-Ferrer, I., Paulus, A., Yang, Y., Swanberg, M., Deierborg, T., & Boza‐Serrano, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00488 · Cited by 706 · see citing works
Neuroinflammation as a common feature of neurodegenerative disorders
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 · see citing works
“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…”
MethodGraeber, M. B. (2010) · Science · doi:10.1126/science.1190929 · Cited by 608 · see citing works
Translocator protein 18 kDa (TSPO): Molecular sensor of brain injury and repair
Chen, M.-K., & Guilarte, T. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.12.004 · Cited by 506 · see citing works
“…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.,…”
BackgroundMethodInfluentialMicroglial activation and amyloid deposition in mild cognitive impairment: A PET study
Okello, A., Edison, P., Archer, H. A., Turkheimer, F. E., Kennedy, J., Bullock, R., Walker, Z., Kennedy, A., Fox, N., Rossor, M., et al. (2009) · Neurology · doi:10.1212/01.wnl.0000338622.27876.0d · Cited by 367 · see citing works
Self-citationVenneti, S., Lopresti, B. J., & Wiley, C. A. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.10.002 · Cited by 373 · see citing works
Inflammation in ALS/FTD pathogenesis
McCauley, M. E., & Baloh, R. H. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-1933-9 · Cited by 316 · see citing works
“Neuroinflammation is also a key component of FTD, supported by similar studies showing increased TPSO binding in several affected brain regions, including the cortical frontal, mesial temporal, subcortical regions, prefrontal cortex, hippocampus and parahippocampus in patients compared to controls [26].”
ResultRole of complement in neurodegeneration and neuroinflammation
Bonifati, D. M., & Kishore, U. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.03.007 · Cited by 310 · see citing works
Neuroinflammation in Neurodegenerative Disorders-a Review
Schain, M., & Kreisl, W. C. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0733-2 · Cited by 301 · see citing works
Neuroinflammation in frontotemporal dementia
Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
Microglia and neuroprotection: From in vitro studies to therapeutic applications
Polazzi, E., & Monti, B. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.06.009 · Cited by 260 · see citing works
Kreisl, W. C., Jenko, K. J., Hines, C. S., Lyoo, C. H., Corona, W., Morse, C. L., Zoghbi, S. S., Hyde, T. M., Kleinman, J. E., Pike, V. W., et al. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.131 · Cited by 251 · see citing works
PET Imaging of Neuroinflammation in Neurological Disorders
Kreisl, W., Kim, M.-J., Coughlin, J. M., Henter, I., Owen, D. R., & Innis, R. (2020) · Lancet Neurology · doi:10.1016/s1474-4422(20)30346-x · Cited by 180 · see citing works
Noninvasive Molecular Imaging of Neuroinflammation
Jacobs, A. H., Tavitian, B., & the INMiND consortium (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.53 · Cited by 245 · see citing works
“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 · see citing works
“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 · see citing works
The impact of high and low dose ionising radiation on the central nervous system
Betlazar, C., Middleton, R., Banati, R., & Liu, G.-J. (2016) · Redox Biology · doi:10.1016/j.redox.2016.08.002 · Cited by 126 · see citing works
“dementia [163], amyotrophic lateral sclerosis [164,165], multiple sclerosis [158,166,167] and brain tumours [168,169].”
BackgroundSelf-citationRecent developments on PET radiotracers for TSPO and their applications in neuroimaging
Zhang, L., Hu, K., Shao, T., Hou, L., Zhang, S., Ye, W., Josephson, L., Meyer, J. H., Zhang, M., Vasdev, N., et al. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.08.006 · Cited by 187 · see citing works
Dupont, A.-C., Largeau, B., Santiago Ribeiro, M., Guilloteau, D., Tronel, C., & Arlicot, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040785 · Cited by 182 · see citing works
Imaging Microglial Activation During Neuroinflammation and Alzheimer’s Disease
Venneti, S., Wiley, C. A., & Kofler, J. (2008) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-008-9142-2 · Cited by 168 · see citing works
“…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 167 · see citing works
A TSPO ligand is protective in a mouse model of multiple sclerosis
Daugherty, D. J., Selvaraj, V., Chechneva, O. V., Liu, X., Pleasure, D., & Deng, W. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202124 · Cited by 158 · see citing works
“…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 · see citing works
Positron Emission Tomography Imaging of Neuroinflammation
Cagnin, A., Kassiou, M., Meikle, S. R., & Banati, R. B. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.04.006 · Cited by 137 · see citing works
“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 · see citing works
Doorduin, J., Klein, H. C., Dierckx, R., James, M. L., Kassiou, M., & de Vries, E. F. J. (2009) · Molecular Imaging and Biology · doi:10.1007/s11307-009-0211-6 · Cited by 131 · see citing works
“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 · see citing works
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 · see citing works
“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 116 · see citing works
“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 · see citing works
Translocator Protein 18 kDa Negatively Regulates Inflammation in Microglia
Bae, K.-R., Shim, H.-J., Balu, D., Kim, S. R., & Yu, S. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9540-6 · Cited by 115 · see citing works
“…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 · see citing works
“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 109 · see citing works
Doorduin, J., de Vries, E. F. J., Dierckx, R. A. J. O., & Klein, H. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786549443 · Cited by 107 · see citing works
Cai, Y., Zhang, Y., Leng, S., Ma, Y., Jiang, Q., Wen, Q., Ju, S., & Hu, J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106426 · Cited by 111 · see citing works
“…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…”
Radford, R. A. W., Morsch, M., Rayner, S. L., Cole, N. J., Pountney, D. L., & Chung, R. S. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00414 · Cited by 102 · see citing works
“…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
Dani, M., Wood, M., Mizoguchi, R., Fan, Z., Walker, Z., Morgan, R., Hinz, R., Biju, M., Kuruvilla, T., Brooks, D. J., et al. (2018) · Brain · doi:10.1093/brain/awy188 · Cited by 270 · see citing works
“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 104 · see citing works
“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 · see citing works
PET/CT in diagnosis of dementia
Berti, V., Pupi, A., & Mosconi, L. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06015.x · Cited by 95 · see citing works
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 · see citing works
“…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).”
Bossù, P., Salani, F., Alberici, A., Archetti, S., Bellelli, G., Galimberti, D., Scarpini, E. A., Spalletta, G., Caltagirone, C., Padovani, A., et al. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-65 · Cited by 91 · see citing works
“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 90 · see citing works
“Similar microglial activation has been described in FTLD, both by in vivo imaging (Cagnin et al., 2004), and by immunohistochemistry (Arnold et al.”
Best, L. A., Ghadery, C., Pavese, N., Tai, Y., & Strafella, A. P. (2019) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-019-0934-y · Cited by 89 · see citing works
Varley, J. A., Brooks, D. J., & Edison, P. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2014.08.105 · Cited by 81 · see citing works
Mirzaei, N., Tang, S. P., Ashworth, S., Coello, C., Plisson, C., Passchier, J., Selvaraj, V., Tyacke, R. J., Nutt, D. J., & Sastre, M. (2016) · Glia · doi:10.1002/glia.22978 · Cited by 82 · see citing works
“…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 82 · see citing works
A predictive coding framework of allostatic–interoceptive overload in frontotemporal dementia
Migeot, J. A., Duran-Aniotz, C. A., Signorelli, C. M., Piguet, O., & Ibáñez, A. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.08.005 · Cited by 76 · see citing works
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 · see citing works
“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 · see citing works
“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].”
MethodCerami, C., Iaccarino, L., & Perani, D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18050993 · Cited by 75 · see citing works
“[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
Chen, H., Kankel, M. W., Su, S. C., Han, S., & Ofengeim, D. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0060-4 · Cited by 74 · see citing works
López‐González, I., Aso, E., Carmona, M., Armand‐Ugón, M., Blanco, R., Naudí, A., Cabré, R., Portero‐Otín, M., Pamplona, R., & Ferrer, I. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000241 · Cited by 71 · see citing works
Masrori, P., Beckers, J., Gossye, H., & Damme, P. V. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00525-z · Cited by 72 · see citing works
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 69 · see citing works
“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 · see citing works
In vivo PET imaging of neuroinflammation in Alzheimer’s disease
Lagarde, J., Sarazin, M., & Bottlaender, M. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1731-x · Cited by 70 · see citing works
“…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 68 · see citing works
“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…”
BackgroundDammann, O. (2006) · Acta Paediatrica · doi:10.1111/j.1651-2227.2007.00097.x · Cited by 68 · see citing works
“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 66 · see citing works
“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 66 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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.-Q., Guo, W.-Z., Fu, Q., Jiao, L.-B., Ma, Y.-Q., & Mi, W. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.02.001 · Cited by 60 · see citing works
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 · see citing works
“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 · see citing works
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 61 · see citing works
Giovannini, M. G., Lana, D., Traini, C., & Vannucchi, M. G. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112358 · Cited by 63 · see citing works
“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 58 · see citing works
Scott, L. L., & Downing, T. G. (2017) · Toxins · doi:10.3390/toxins10010022 · Cited by 57 · see citing works
“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., Tomljanovic, Z., Polly, K., Klein, J., Razlighi, Q., Brickman, A., Lee, S., Stern, Y., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.019 · Cited by 50 · see citing works
“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 · see citing works
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 · see citing works
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 55 · see citing works
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 54 · see citing works
“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 54 · see citing works
Glial biomarkers in human central nervous system disease
Garden, G. A., & Campbell, B. M. (2016) · Glia · doi:10.1002/glia.22998 · Cited by 54 · see citing works
“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 51 · see citing works
“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., Bonnı̀, 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 49 · see citing works
“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 45 · see citing works
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 46 · see citing works
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 48 · see citing works
Banati, R. B., & Hickie, I. B. (2009) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2009.tb02371.x · Cited by 46 · see citing works
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 45 · see citing works
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 · see citing works
“, 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 · see citing works
“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 · see citing works
Neuroimmune Tau Mechanisms: Their Role in the Progression of Neuronal Degeneration
Cortés, N., Andrade, V., Guzmán-Martínez, L., Estrella, M., & Maccioni, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040956 · Cited by 41 · see citing works
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 40 · see citing works
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 · see citing works
“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 39 · see citing works
“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 · see citing works
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 39 · see citing works
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 · see citing works
“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 · see citing works
Azrad, M., Zeineh, N., Weizman, A., Veenman, L., & Gavish, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030594 · Cited by 37 · see citing works
- 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
- Health Sciences › Medicine › Physiology › 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
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
