{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:43:54Z","timestamp":1792669434200,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Alzheimer\u2019s Research UK PhD Scholarships","award":["ARUK-PhD2023-018; 2024-006"],"award-info":[{"award-number":["ARUK-PhD2023-018; 2024-006"]}]},{"DOI":"10.13039\/501100017506","name":"Alzheimer\u2019s Society","doi-asserted-by":"publisher","award":["694"],"award-info":[{"award-number":["694"]}],"id":[{"id":"10.13039\/501100017506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UKDRI-2203"],"award-info":[{"award-number":["UKDRI-2203"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Race Against Dementia; Alzheimer\u2019s Research UK","award":["ARUK-RADF2021A-010"],"award-info":[{"award-number":["ARUK-RADF2021A-010"]}]},{"name":"Kissick Family Foundation Frontotemporal Dementia Grant Program","award":["KFF-FTD-3449204717"],"award-info":[{"award-number":["KFF-FTD-3449204717"]}]},{"name":"Dementias Platform UK; Medical Research Council","award":["MC_UU_00030\/14; MR\/T033371\/1"],"award-info":[{"award-number":["MC_UU_00030\/14; MR\/T033371\/1"]}]},{"name":"Wellcome Trust","award":["103838; 220258"],"award-info":[{"award-number":["103838; 220258"]}]},{"name":"the Cambridge University Centre for Parkinson-Plus","award":["RG95450"],"award-info":[{"award-number":["RG95450"]}]},{"name":"National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre","award":["BRC-1215-20014; NIHR203312"],"award-info":[{"award-number":["BRC-1215-20014; NIHR203312"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brain inflammation is a key feature of frontotemporal dementia (FTD). Positron emission tomography (PET) of the 18\u00a0kDa translocator protein (TSPO) is widely used as an in vivo proxy for neuroinflammation, but whether the elevated signal reflects microglial, astrocytic or vascular pathology remains controversial, and this has not previously been resolved in FTD using matched\n                    <jats:italic>ante mortem<\/jats:italic>\n                    imaging and\n                    <jats:italic>post-mortem<\/jats:italic>\n                    tissue. We paired\n                    <jats:italic>ante mortem<\/jats:italic>\n                    [\n                    <jats:sup>11<\/jats:sup>\n                    C]PK11195 TSPO\u2013PET with quantitative\n                    <jats:italic>post-mortem<\/jats:italic>\n                    neuropathology in 10 individuals with FTD (5 FTLD-tau, 5 FTLD\u2013TDP) and 5 age- and sex-matched controls, combining CD68 immunohistochemistry across 17 brain regions, multiplex immunofluorescence pairing TSPO with microglial\/macrophagic (IBA1, CD68), astrocytic (GFAP) and endothelial (CD31) markers in three frontotemporal cortical regions, and three-dimensional single-cell reconstruction of individual microglia. CD68 area fraction was elevated in FTD relative to controls, predominantly in white matter, and was positively associated with regional TSPO\u2013PET-binding potential across the cohort (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    = 8.66,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001), with comparable slopes in FTLD-tau and FTLD\u2013TDP. Total tissue TSPO-area fraction was likewise increased in FTD and tracked regional PET binding in two independently processed slide sets. Of the four cell-type markers, only the CD68\u2013TSPO co-localised fraction was positively associated with the PET signal (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    = +0.0041,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.015,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>FDR<\/jats:sub>\n                    = 0.062), with null or negative associations for IBA1, GFAP and CD31. At single-cell resolution, IBA1+ microglia that were also CD68+ carried more absolute TSPO and were larger than CD68\u2212 microglia, without an increase in the TSPO fraction of cell volume. The elevated TSPO\u2013PET signal in FTD, therefore, likely reflects an increased burden of CD68+ phagocytic microglia rather than TSPO expression in other cell types, supporting TSPO\u2013PET as a microglial-burden biomarker across both FTLD-tau and FTLD\u2013TDP.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-03103-5","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:22:59Z","timestamp":1792668179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TSPO\u2013PET binding in vivo reflects increased phagocytic microglia at post mortem in people with frontotemporal dementia"],"prefix":"10.1007","volume":"152","author":[{"given":"Davi S.","family":"Vontobel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei Onn","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehtap","family":"Bacioglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Maddison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Adamski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Goddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah L.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Crook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Fryer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasvi","family":"Wijesinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Aigbirhio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Avezov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieren S. J.","family":"Allinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Quaegebeur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Spillantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"3103_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26093927","volume":"26","author":"P Alster","year":"2025","unstructured":"Alster P, Madetko-Alster N (2025) The genetic background of the immunological and inflammatory aspects of progressive supranuclear palsy. Int J Mol Sci 26:3927. https:\/\/doi.org\/10.3390\/ijms26093927","journal-title":"Int J Mol Sci"},{"key":"3103_CR2","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/brain\/awae234","volume":"148","author":"J Appleton","year":"2025","unstructured":"Appleton J, Finn Q, Zanotti-Fregonara P, Yu M, Faridar A, Nakawah MO et al (2025) Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer\u2019s disease. Brain 148:119\u2013132. https:\/\/doi.org\/10.1093\/brain\/awae234","journal-title":"Brain"},{"key":"3103_CR3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-013187","volume":"7","author":"WR Bevan-Jones","year":"2017","unstructured":"Bevan-Jones WR, Surendranathan A, Passamonti L, V\u00e1zquez Rodr\u00edguez P, Arnold R, Mak E et al (2017) Neuroimaging of inflammation in memory and related other disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses. BMJ Open 7:e013187. https:\/\/doi.org\/10.1136\/bmjopen-2016-013187","journal-title":"BMJ Open"},{"key":"3103_CR4","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1093\/brain\/awaa033","volume":"143","author":"WR Bevan-Jones","year":"2020","unstructured":"Bevan-Jones WR, Cope TE, Jones PS, Kaalund SS, Passamonti L, Allinson K et al (2020) Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum. Brain 143:1010\u20131026. https:\/\/doi.org\/10.1093\/brain\/awaa033","journal-title":"Brain"},{"key":"3103_CR5","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41582-019-0231-z","volume":"15","author":"F Bright","year":"2019","unstructured":"Bright F, Werry EL, Dobson-Stone C, Piguet O, Ittner LM, Halliday GM et al (2019) Neuroinflammation in frontotemporal dementia. Nat Rev Neurol 15:540\u2013555. https:\/\/doi.org\/10.1038\/s41582-019-0231-z","journal-title":"Nat Rev Neurol"},{"key":"3103_CR6","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1365-2990.2008.01006.x","volume":"35","author":"M Cosenza-Nashat","year":"2009","unstructured":"Cosenza-Nashat M, Zhao ML, Suh HS, Morgan J, Natividad R, Morgello S et al (2009) Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol 35:306\u2013328. https:\/\/doi.org\/10.1111\/j.1365-2990.2008.01006.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"3103_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.bbi.2023.07.023","volume":"113","author":"LJ De Picker","year":"2023","unstructured":"De Picker LJ, Morrens M, Branchi I, Haarman BCM, Terada T, Kang MS et al (2023) TSPO PET brain inflammation imaging: a transdiagnostic systematic review and meta-analysis of 156 case-control studies. Brain Behav Immun 113:415\u2013431. https:\/\/doi.org\/10.1016\/j.bbi.2023.07.023","journal-title":"Brain Behav Immun"},{"key":"3103_CR8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s40478-014-0090-1","volume":"2","author":"KJ Doorn","year":"2014","unstructured":"Doorn KJ, Moors T, Drukarch B, van de Berg WDJ, Lucassen PJ, van Dam AM (2014) Microglial phenotypes and Toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson\u2019s disease patients. Acta Neuropathol Commun 2:90. https:\/\/doi.org\/10.1186\/s40478-014-0090-1","journal-title":"Acta Neuropathol Commun"},{"key":"3103_CR9","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.biochi.2024.07.003","volume":"224","author":"LH Fairley","year":"2024","unstructured":"Fairley LH, Lai KO, Grimm A, Eckert A, Barron AM (2024) The mitochondrial translocator protein (TSPO) in Alzheimer\u2019s disease: therapeutic and immunomodulatory functions. Biochimie 224:120\u2013131. https:\/\/doi.org\/10.1016\/j.biochi.2024.07.003","journal-title":"Biochimie"},{"key":"3103_CR10","doi-asserted-by":"publisher","first-page":"3685","DOI":"10.1093\/brain\/awv288","volume":"138","author":"Z Fan","year":"2015","unstructured":"Fan Z, Okello AA, Brooks DJ, Edison P (2015) Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer\u2019s disease. Brain 138:3685\u20133698. https:\/\/doi.org\/10.1093\/brain\/awv288","journal-title":"Brain"},{"key":"3103_CR11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s00401-024-02822-x","volume":"148","author":"EF Garland","year":"2024","unstructured":"Garland EF, Antony H, Kulagowska L, Scott T, Rogien C, Bottlaender M et al (2024) The microglial translocator protein (TSPO) in Alzheimer\u2019s disease reflects a phagocytic phenotype. Acta Neuropathol 148:62. https:\/\/doi.org\/10.1007\/s00401-024-02822-x","journal-title":"Acta Neuropathol"},{"key":"3103_CR12","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1212\/WNL.0b013e31821103e6","volume":"76","author":"ML Gorno-Tempini","year":"2011","unstructured":"Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF et al (2011) Classification of primary progressive aphasia and its variants. Neurology 76:1006\u20131014. https:\/\/doi.org\/10.1212\/WNL.0b013e31821103e6","journal-title":"Neurology"},{"key":"3103_CR13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41572-023-00447-0","volume":"9","author":"M Grossman","year":"2023","unstructured":"Grossman M, Seeley WW, Boxer AL, Hillis AE, Knopman DS, Ljubenov PA et al (2023) Frontotemporal lobar degeneration. Nat Rev Dis Primers 9:40. https:\/\/doi.org\/10.1038\/s41572-023-00447-0","journal-title":"Nat Rev Dis Primers"},{"key":"3103_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108048","volume":"234","author":"TR Guilarte","year":"2022","unstructured":"Guilarte TR, Rodichkin AN, McGlothan JL, Acanda De La Rocha AM, Azzam DJ (2022) Imaging neuroinflammation with TSPO: a new perspective on the cellular sources and subcellular localization. Pharmacol Ther 234:108048. https:\/\/doi.org\/10.1016\/j.pharmthera.2021.108048","journal-title":"Pharmacol Ther"},{"key":"3103_CR15","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jneuroim.2017.04.007","volume":"309","author":"DAE Hendrickx","year":"2017","unstructured":"Hendrickx DAE, van Eden CG, Schuurman KG, Hamann J, Huitinga I (2017) Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology. J Neuroimmunol 309:12\u201322. https:\/\/doi.org\/10.1016\/j.jneuroim.2017.04.007","journal-title":"J Neuroimmunol"},{"key":"3103_CR16","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/mp.2017.246","volume":"23","author":"KE Hopperton","year":"2018","unstructured":"Hopperton KE, Mohammad D, Tr\u00e9panier MO, Giuliano V, Bazinet RP (2018) Markers of microglia in post-mortem brain samples from patients with Alzheimer\u2019s disease: a systematic review. Mol Psychiatry 23:177\u2013198. https:\/\/doi.org\/10.1038\/mp.2017.246","journal-title":"Mol Psychiatry"},{"key":"3103_CR17","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1093\/jnen\/60.6.647","volume":"60","author":"K Ishizawa","year":"2001","unstructured":"Ishizawa K, Dickson DW (2001) Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration. J Neuropathol Exp Neurol 60:647\u2013657. https:\/\/doi.org\/10.1093\/jnen\/60.6.647","journal-title":"J Neuropathol Exp Neurol"},{"key":"3103_CR18","doi-asserted-by":"publisher","DOI":"10.1111\/jon.70002","volume":"35","author":"P Jensen","year":"2025","unstructured":"Jensen P, Ozenne B, Meden P, Feng L, Thomsen G, Knudsen L et al (2025) Poststroke translocator protein expression dynamics and correlations to chronic infarction: a [123I]-CLINDE-SPECT study. J Neuroimaging 35:e70002. https:\/\/doi.org\/10.1111\/jon.70002","journal-title":"J Neuroimaging"},{"key":"3103_CR19","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1002\/acn3.50802","volume":"6","author":"MJ Kim","year":"2019","unstructured":"Kim MJ, McGwier M, Jenko KJ, Snow J, Morse C, Zoghbi SS et al (2019) Neuroinflammation in frontotemporal lobar degeneration revealed by 11C-PBR28 PET. Ann Clin Transl Neurol 6:1327\u20131331. https:\/\/doi.org\/10.1002\/acn3.50802","journal-title":"Ann Clin Transl Neurol"},{"key":"3103_CR20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.neurobiolaging.2016.04.011","volume":"44","author":"WC Kreisl","year":"2016","unstructured":"Kreisl WC, Lyoo CH, Liow JS, Wei M, Snow J, Page E et al (2016) 11C-PBR28 binding to translocator protein increases with progression of Alzheimer\u2019s disease. Neurobiol Aging 44:53\u201361. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2016.04.011","journal-title":"Neurobiol Aging"},{"key":"3103_CR21","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1002\/ana.25911","volume":"88","author":"M Malpetti","year":"2020","unstructured":"Malpetti M, Passamonti L, Rittman T, Jones PS, V\u00e1zquez Rodr\u00edguez P, Bevan-Jones WR et al (2020) Neuroinflammation and tau colocalize in vivo in progressive supranuclear palsy. Ann Neurol 88:1194\u20131204. https:\/\/doi.org\/10.1002\/ana.25911","journal-title":"Ann Neurol"},{"key":"3103_CR22","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1136\/jnnp-2020-325549","volume":"92","author":"M Malpetti","year":"2021","unstructured":"Malpetti M, Passamonti L, Jones PS, Street D, Rittman T, Fryer TD et al (2021) Neuroinflammation predicts disease progression in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 92:769\u2013775. https:\/\/doi.org\/10.1136\/jnnp-2020-325549","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"3103_CR23","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1093\/brain\/awad078","volume":"146","author":"M Malpetti","year":"2023","unstructured":"Malpetti M, Cope TE, Street D, Jones PS, Hezemans FH, Mak E et al (2023) Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia. Brain 146:3221\u20133231. https:\/\/doi.org\/10.1093\/brain\/awad078","journal-title":"Brain"},{"key":"3103_CR24","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/978-1-0716-3774-6_12","volume-title":"Biomarkers for Alzheimer's disease drug development","author":"M Malpetti","year":"2024","unstructured":"Malpetti M, Franzmeier N, Brendel M (2024) PET imaging to measure neuroinflammation in vivo. In: Perneczky R (ed) Biomarkers for Alzheimer\u2019s disease drug development, vol vol 2785. Humana, New York, NY, pp 177\u2013193. https:\/\/doi.org\/10.1007\/978-1-0716-3774-6_12"},{"key":"3103_CR25","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1002\/mds.29924","volume":"39","author":"M Malpetti","year":"2024","unstructured":"Malpetti M, Roemer SN, Harris S, Gross M, Gn\u00f6rich J, Stephens A et al (2024) Neuroinflammation parallels 18F-PI-2620 positron emission tomography patterns in primary 4-repeat tauopathies. Mov Disord 39:1480\u20131492. https:\/\/doi.org\/10.1002\/mds.29924","journal-title":"Mov Disord"},{"key":"3103_CR26","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.jml.2017.01.001","volume":"94","author":"H Matuschek","year":"2017","unstructured":"Matuschek H, Kliegl R, Vasishth S, Baayen H, Bates D (2017) Balancing type I error and power in linear mixed models. J Mem Lang 94:305\u2013315. https:\/\/doi.org\/10.1016\/j.jml.2017.01.001","journal-title":"J Mem Lang"},{"key":"3103_CR27","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s004010000284","volume":"101","author":"M Mittelbronn","year":"2001","unstructured":"Mittelbronn M, Dietz K, Schluesener HJ, Meyermann R (2001) Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude. Acta Neuropathol 101:249\u2013255. https:\/\/doi.org\/10.1007\/s004010000284","journal-title":"Acta Neuropathol"},{"key":"3103_CR28","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/978-3-030-51140-1_13","volume-title":"Frontotemporal dementias","author":"M Neumann","year":"2021","unstructured":"Neumann M, Lee EB, Mackenzie IR (2021) Frontotemporal lobar degeneration TDP-43-immunoreactive pathological subtypes: clinical and mechanistic significance. In: Ghetti B, Buratti E, Boeve B, Rademakers R (eds) Frontotemporal dementias, vol vol 1281. Springer, Cham, pp 201\u2013217. https:\/\/doi.org\/10.1007\/978-3-030-51140-1_13"},{"key":"3103_CR29","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s00259-020-05166-2","volume":"49","author":"E Nutma","year":"2021","unstructured":"Nutma E, Ceyz\u00e9riat K, Amor S, Tsartsalis S, Millet P, Owen DR et al (2021) Cellular sources of TSPO expression in healthy and diseased brain. Eur J Nucl Med Mol Imaging 49:146\u2013163. https:\/\/doi.org\/10.1007\/s00259-020-05166-2","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"3103_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40937-z","volume":"14","author":"E Nutma","year":"2023","unstructured":"Nutma E, Fancy N, Weinert M, Tsartsalis S, Marzin MC, Muirhead RCJ et al (2023) Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases. Nat Commun 14:5247. https:\/\/doi.org\/10.1038\/s41467-023-40937-z","journal-title":"Nat Commun"},{"key":"3103_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03519-y","volume":"22","author":"M Nylund","year":"2025","unstructured":"Nylund M, Lehto J, Matilainen M, Rajander J, Wahlroos S, Sucksdorff M et al (2025) Longitudinal accumulation of glial activation measured by TSPO-PET predicts later brain atrophy in multiple sclerosis. J Neuroinflammation 22:200. https:\/\/doi.org\/10.1186\/s12974-025-03519-y","journal-title":"J Neuroinflammation"},{"key":"3103_CR32","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/mds.28395","volume":"36","author":"C Palleis","year":"2021","unstructured":"Palleis C, Sauerbeck J, Beyer L, Harris S, Schmitt J, Morenas-Rodriguez E et al (2021) In vivo assessment of neuroinflammation in 4-repeat tauopathies. Mov Disord 36:883\u2013894. https:\/\/doi.org\/10.1002\/mds.28395","journal-title":"Mov Disord"},{"key":"3103_CR33","doi-asserted-by":"publisher","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","volume":"110","author":"RC Paolicelli","year":"2022","unstructured":"Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B et al (2022) Microglia states and nomenclature: a field at its crossroads. Neuron 110:3458\u20133483. https:\/\/doi.org\/10.1016\/j.neuron.2022.10.020","journal-title":"Neuron"},{"key":"3103_CR34","doi-asserted-by":"publisher","first-page":"e1989","DOI":"10.1212\/WNL.0000000000005610","volume":"90","author":"L Passamonti","year":"2018","unstructured":"Passamonti L, V\u00e1zquez Rodr\u00edguez P, Hong YT, Allinson KSJ, Bevan-Jones WR, Williamson D et al (2018) [11C]PK11195 binding in Alzheimer disease and progressive supranuclear palsy. Neurology 90:e1989\u2013e1996. https:\/\/doi.org\/10.1212\/WNL.0000000000005610","journal-title":"Neurology"},{"key":"3103_CR35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12974-023-02866-y","volume":"20","author":"JD Quick","year":"2023","unstructured":"Quick JD, Silva C, Wong JH, Lim KL, Reynolds R, Barron AM et al (2023) Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration. J Neuroinflammation 20:185. https:\/\/doi.org\/10.1186\/s12974-023-02866-y","journal-title":"J Neuroinflammation"},{"key":"3103_CR36","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1093\/brain\/awr179","volume":"134","author":"K Rascovsky","year":"2011","unstructured":"Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456\u20132477. https:\/\/doi.org\/10.1093\/brain\/awr179","journal-title":"Brain"},{"key":"3103_CR37","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1177\/0271678X17742004","volume":"39","author":"G Rizzo","year":"2019","unstructured":"Rizzo G, Veronese M, Tonietto M, Bodini B, Stankoff B, Wimberley C et al (2019) Generalization of endothelial modelling of TSPO PET imaging: considerations on tracer affinities. J Cereb Blood Flow Metab 39:874\u2013885. https:\/\/doi.org\/10.1177\/0271678X17742004","journal-title":"J Cereb Blood Flow Metab"},{"key":"3103_CR38","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf467","volume":"7","author":"NL Shapiro","year":"2025","unstructured":"Shapiro NL, Jones PS, Mak E, Tsvetanov KA, Goddard J, Vontobel DS et al (2025) Inflammation PET and plasma neurofilament light predict survival in people with progressive supranuclear palsy. Brain Commun 7:fcaf467. https:\/\/doi.org\/10.1093\/braincomms\/fcaf467","journal-title":"Brain Commun"},{"key":"3103_CR39","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.2967\/jnumed.108.050583","volume":"49","author":"G Tomasi","year":"2008","unstructured":"Tomasi G, Edison P, Bertoldo A, Roncaroli F, Singh P, Gerhard A et al (2008) Novel reference region model reveals increased microglial and reduced vascular binding of 11C-(R)-PK11195 in patients with Alzheimer\u2019s disease. J Nucl Med 49:1249\u20131256. https:\/\/doi.org\/10.2967\/jnumed.108.050583","journal-title":"J Nucl Med"},{"key":"3103_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64540-6","volume":"16","author":"E Vokali","year":"2025","unstructured":"Vokali E, Chevalier E, Dreyfus N, Charmey D, Melly T, Kocher J et al (2025) Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology. Nat Commun 16:9358. https:\/\/doi.org\/10.1038\/s41467-025-64540-6","journal-title":"Nat Commun"},{"key":"3103_CR41","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1093\/brain\/awaf078","volume":"148","author":"SS Wijesinghe","year":"2025","unstructured":"Wijesinghe SS, Rowe JB, Mason HD, Allinson KSJ, Thomas R, Vontobel DS et al (2025) Post-mortem validation of in vivo TSPO PET as a microglial biomarker. Brain 148:1904\u20131910. https:\/\/doi.org\/10.1093\/brain\/awaf078","journal-title":"Brain"},{"key":"3103_CR42","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12974-020-01907-0","volume":"17","author":"IOC Woollacott","year":"2020","unstructured":"Woollacott IOC, Toomey CE, Strand C, Courtney R, Benson BC, Rohrer JD et al (2020) Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration. J Neuroinflammation 17:234. https:\/\/doi.org\/10.1186\/s12974-020-01907-0","journal-title":"J Neuroinflammation"},{"key":"3103_CR43","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1038\/jcbfm.2012.59","volume":"32","author":"M Yaqub","year":"2012","unstructured":"Yaqub M, van Berckel BNM, Schuitemaker A, Hinz R, Turkheimer FE, Tomasi G et al (2012) Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies. J Cereb Blood Flow Metab 32:1600\u20131608. https:\/\/doi.org\/10.1038\/jcbfm.2012.59","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03103-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03103-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03103-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:23:01Z","timestamp":1792668181000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03103-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3103"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-03103-5","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"3 August 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.T.O. has received honoraria for work as DSMB chair or member for TauRx, Axon, Eisai, and Novo Nordisk, and has acted as a consultant for Biogen and Roche, and has received research support from Alliance Medical and Merck. J.B.R. is a non-remunerated trustee of the Guarantors of Brain, Darwin College, and the PSP Association (UK). He has provided consultancy unrelated to this work to Asceneuron, Astronautx, Alector, Astex, AviadoBio, Booster Therapeutics, Boehringer Ingelheim, Clinical Ink, Curasen, CumulusNeuro, Wave, SVHealth, Prevail, UCB and has research grants from AZ-Medimmune, Janssen, and Lilly as industry partners in the Dementias Platform UK. M.M. has acted as a consultant for Astex Pharmaceuticals.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocols were approved by the National Research Ethics Service\u2019s East of England Cambridge Central Committee and the UK Administration of Radioactive Substances Advisory Committee (Neuropathology Research in Dementia protocol, Research Ethics Committee reference 16\/WA\/0240; Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD), Research Ethics Committee reference 13\/EE\/0104). All procedures were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments. Post-mortem human brain tissue was provided by the Cambridge Brain Bank.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from all participants.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written consent covering the use of donated tissue and associated data in research and publication was obtained from participants during life and\/or from their next of kin. No individually identifiable participant information is presented.","order":4,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"59"}}