Neuroinflammation predicts disease progression in progressive supranuclear palsy
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Abstract
Introduction: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP. Methods: Seventeen patients with PSP–Richardson’s syndrome underwent a baseline multimodal imaging assessment, including [ 11 C]PK11195 positron emission tomography (PET) to index microglial activation, [ 18 F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals’ estimated rate of progression to identify the prognostic value of baseline imaging markers. Results: PCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression. Conclusions: Molecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.
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Baseline PK-PET in AD and PSP was able to predict clinical progression.
“while baseline PK-PET in AD and PSP was able to predict clinical progression [221, 222]”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [221]
Subcortical tau pathology and microglial activation positively correlated with clinical severity and could predict disease progression in PSP.
“Additionally, subcortical tau pathology and microglial activation positively correlated with clinical severity376,378,379 and could predict disease progression in PSP.379”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [379]
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Molecular pathology and synaptic loss in primary tauopathies: an 18F-AV-1451 and 11C-UCB-J PET study
Holland, N., Malpetti, M., Rittman, T., Mak, E. E., Passamonti, L., Kaalund, S. S., Hezemans, F. H., Jones, P. S., Savulich, G., Hong, Y. T., et al. (2022) · Brain · doi:10.1093/brain/awab282 · Cited by 39 · see citing works
“As the disease progresses, other pathological processes may contribute to synaptic loss, such as inflammation, another predictor of prognosis and mediator of synaptic loss.(60) Therefore, there is not a simple linear relationship”
Self-citationPost-mortem validation of in vivo TSPO PET as a microglial biomarker
Wijesinghe, S. S., Rowe, J. B., Mason, H. D., Allinson, K. S. J., Thomas, R., Vontobel, D. S., Fryer, T. D., Hong, Y. T., Bacioglu, M., Spillantini, M. G., et al. (2025) · Brain · doi:10.1093/brain/awaf078 · Cited by 37 · see citing works
Self-citationClinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants
Street, D., Malpetti, M., Rittman, T., Ghosh, B. C. P., Murley, A. G., Coyle-Gilchrist, I. T. S., Passamonti, L., & Rowe, J. B. (2021) · Brain Communications · doi:10.1093/braincomms/fcab206 · Cited by 37 · see citing works
Self-citationBäckström, D. C., Granåsen, G., Mo, S. J., Riklund, K., Trupp, M., Zetterberg, H., Blennow, K., Forsgren, L., & Domellöf, M. E. (2022) · Brain Communications · doi:10.1093/braincomms/fcac040 · Cited by 37 · see citing works
Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?
Krey, L., Huber, M. K., Höglinger, G. U., & Wegner, F. (2021) · Brain Sciences · doi:10.3390/brainsci11121654 · Cited by 31 · see citing works
Burnham, S. C., Iaccarino, L., Pontecorvo, M. J., Fleisher, A., Lu, M., Collins, E. C., & Devous, M. D. (2023) · Brain Communications · doi:10.1093/braincomms/fcad305 · Cited by 29 · see citing works
Progressive Supranuclear Palsy Syndrome: An Overview
Ichikawa-Escamilla, E., Velasco-Martínez, R. A., & Adalid-Peralta, L. V. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.04.008 · Cited by 26 · see citing works
“Neuroinflammation was proposed to increase PSP-S severity and progression (Malpetti et al., 2021).”
BackgroundMalpetti, M., Roemer, S. N., Harris, S., Groß, M., Gnörich, J. S., Stephens, A. W., Dewenter, A., Steward, A., Biel, D., Dehsarvi, A., et al. (2024) · Movement Disorders · doi:10.1002/mds.29924 · Cited by 24 · see citing works
Self-citationThe emerging role of LRRK2 in tauopathies
Herbst, S., Lewis, P. A., & Morris, H. R. (2022) · Clinical Science · doi:10.1042/cs20220067 · Cited by 23 · see citing works
Liu, F., Li, X., Lu, J., Wu, P., Li, L., Liang, X., Ju, Z., Jiao, F., Chen, M., Ge, J., et al. (2022) · Movement Disorders · doi:10.1002/mds.29159 · Cited by 23 · see citing works
“Neuroinflammation has been previously associated with the presence of tau pathology— being in turn linked to clinical severity(22) and the clinical trajectories of PSP.(23) Neuroinflammatory reactions have also been implicated in the pathogenesis of FIG.”
BackgroundNeurophysiological consequences of synapse loss in progressive supranuclear palsy
Adams, N. E., Jafarian, A., Perry, A., Rouse, M. A., Shaw, A. D., Murley, A. G., Cope, T. E., Bevan-Jones, W. R., Passamonti, L., Street, D., et al. (2023) · Brain · doi:10.1093/brain/awac471 · Cited by 21 · see citing works
“…modelling approach could include other subject-specific markers of pathology, such as magnetic resonance spectroscopy estimates of principal neurotransmitters, 48 or PET ligand markers for the severity of amyloid or Tau burden 58 or neuroinflammation; 59 or even post-mortem quantitative pathology.”
Self-citationValidation of the new pathology staging system for progressive supranuclear palsy
Briggs, M., Allinson, K. S. J., Malpetti, M., Spillantini, M. G., Rowe, J. B., & Kaalund, S. S. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02298-z · Cited by 21 · see citing works
“To overcome this limitation we adjusted for the time interval in our analysis, taking advantage of the longitudinal data available for most patients in order to impute the scores at death [18].”
MethodSelf-citationBivona, G., Iemmolo, M., Piccoli, T., Agnello, L., Sasso, B. L., Ciaccio, M., & Ghersi, G. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11195498 · Cited by 20 · see citing works
Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?
Prange, S., Theis, H., Banwinkler, M., & van Eimeren, T. (2022) · Brain Sciences · doi:10.3390/brainsci12091146 · Cited by 21 · see citing works
Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy
Couto, B., Forrest, S. L., Fearon, C., Lee, S., Knott, S., Li, J., Fox, S. H., Tartaglia, M. C., Lang, A. E., & Kovács, G. G. (2025) · Brain · doi:10.1093/brain/awaf135 · Cited by 16 · see citing works
Palleis, C., Franzmeier, N., Weidinger, E., Bernhardt, A. M., Katzdobler, S., Wall, S., Ferschmann, C., Harris, S., Schmitt, J., Schuster, S., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207901 · Cited by 18 · see citing works
Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes
Murley, A. G., Tsvetanov, K. A., Rouse, M. A., Jones, P. S., Sværke, K., Li, W., Carpenter, A., & Rowe, J. B. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.10.012 · Cited by 16 · see citing works
“Neuroinflammation has been identified by TSPO-ligand position emission tomography, in bvFTD, PPA and PSP ( Bevan-Jones et al., 2020 ; Malpetti et al., 2020 ), where it is not only elevated but also prognostic of a more rapid decline ( Malpetti et al., 2020 ).”
BackgroundSelf-citationPositron Emission Tomography in Animal Models of Tauopathies
Cao, L., Kong, Y., Ji, B., Ren, Y., Guan, Y., & Ni, R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.761913 · Cited by 14 · see citing works
Enhanced drug delivery by a prodrug approach effectively relieves neuroinflammation in mice
Montaser, A. B., Kuiri, J., Natunen, T., Hruška, P., Potěšil, D., Auriola, S. O. K., Hiltunen, M. O., Terasaki, T., Lehtonen, M., Jalkanen, A. J., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121088 · Cited by 15 · see citing works
PET Imaging to Measure Neuroinflammation In Vivo
Malpetti, M., Franzmeier, N., & Brendel, M. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3774-6_12 · Cited by 14 · see citing works
Self-citationBiomarkers of disease progression in progressive supranuclear palsy for use in clinical trials
Marotta, C., Sinclair, B., O'Brien, T. J., & Vivash, L. E. (2024) · Brain Communications · doi:10.1093/braincomms/fcaf022 · Cited by 14 · see citing works
“Malpetti et al. 63 found that greater 18 F-flortaucipir binding potential in the midbrain, pons, thalamus, dentate nucleus and cerebellar white matter correlated with faster progression on the PSPRS.”
InfluentialCarlos, A. F., Tosakulwong, N., Weigand, S. D., Buciuc, M., Ali, F., Clark, H. M., Botha, H., Utianski, R. L., Machulda, M. M., Schwarz, C. G., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac108 · Cited by 14 · see citing works
4R-tau seeding activity reveals molecular subtypes in progressive supranuclear palsy
Martínez-Valbuena, I., Lee, S., Santamaría, E., Fernández‐Irigoyen, J., Forrest, S. L., Zampar, S., Li, J. Y., Tanaka, H., Couto, B., Reyes, N. G. D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67744-y · Cited by 26 · see citing works
4R-Tau seeding activity unravels molecular subtypes in patients with Progressive Supranuclear PalsyPreprint
Martínez-Valbuena, I., Lee, S., Santamaría, E., Fernández‐Irigoyen, J., Forrest, S. L., Li, J., Tanaka, H., Couto, B., Reyes, N. G. D., Qamar, S. H., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.28.559953 · Cited by 11 · see citing works
Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy
Rosina, M., Veltri, F., Nesci, V., Bissacco, J., Bovenzi, R., Mascioli, D., Simonetta, C., Zenuni, H., Maftei, D., Marano, M., et al. (2024) · Movement Disorders · doi:10.1002/mds.30009 · Cited by 10 · see citing works
PET/CT in Movement Disorders: Update
Nerattini, M., Abenavoli, E. M., & Berti, V. (2025) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2025.03.007 · Cited by 10 · see citing works
Strobel, J., Müller, H.-P., Ludolph, A. C., Beer, A. J., Sollmann, N., & Kassubek, J. (2023) · Cells · doi:10.3390/cells12242776 · Cited by 10 · see citing works
Frost, B. E., Rowe, J. B., Akinyemi, R., Abisambra, J. F., Ashton, N. J., Brendel, M., Buée, L., Butler, D., Carrillo, M. C., Chung, P. S., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70078 · Cited by 9 · see citing works
“55 95 In an autopsy sample, in vivo regional [ 18 F]PI-2620tau-PETsignalscorrelatedstronglywithanabundanceoffibrillar tau in a small sample of people with and without PSP. 89 In another autopsy sample of people with PSP, AT8 tau-positive neurons, but not astrocytes, were the driver of [ 18 F]PI-2620 autoradiography si…”
InfluentialSelf-citationMultifactorial etiology of progressive supranuclear palsy (PSP): the genetic component
Müller, U., Höglinger, G. U., & Dickson, D. W. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02898-z · Cited by 10 · see citing works
Striatal dopaminergic lesions contributed to the disease severity in progressive supranuclear palsy
Chen, M., Lu, J., Li, X., Jiao, F., Zuo, C., Wang, J., Liu, F., & Yang, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.998255 · Cited by 9 · see citing works
“With regard to imaging features, the bindings of several tau tracers in the midbrain were related with the disease severity of PSP (Kepe et al., 2013; Brendel et al., 2017; PerezSoriano et al., 2017; Schirinzi et al., 2018; Malpetti et al., 2021).”
BackgroundPathomechanisms of depression in progressive supranuclear palsy
Jellinger, K. A. (2023) · Journal of Neural Transmission · doi:10.1007/s00702-023-02621-w · Cited by 7 · see citing works
“With regard to the importance of neuroinflammation in the pathogenesis of PSP, the use of cytokine inhibitors, antiinflammatory agents and immunomodulatory approaches may be useful for an effective (or even disease-modifying) treatment of this deleterious disease (Malpetti et al. 2021), as were proposed TNFα inhibitor…”
BackgroundBrain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy
Quattrone, A., Franzmeier, N., Huppertz, H., Seneca, N. M., Petzold, G. C., Spottke, A. E., Levin, J., Prudlo, J., Düzel, E., the PASSPORT Study Group, T. A. I., et al. (2025) · Movement Disorders · doi:10.1002/mds.70026 · Cited by 6 · see citing works
Qu, J., Qu, Y., Zhu, R., Wu, Y., Xu, G., & Wang, D. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14901 · Cited by 6 · see citing works
“63,70,71 By employing the PLS regression technique to correlate neuroimaging phenotypes with gene expression patterns in the AHBA dataset, we found a group of genes in PLS1 with markedly positive or negative impacts that correlate with the MSN alterations in patients with PSP. Genes included in the…”
MethodAlster, P., van Eimeren, T., & Madetko‐Alster, N. (2025) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2025.107939 · Cited by 5 · see citing works
Shapiro, N. L., Jones, P. S., Mak, E., Tsvetanov, K. A., Goddard, J., Vontobel, D. S., Durcan, R., Chouliaras, L., Fryer, T. D., Hong, Y. T., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf467 · Cited by 5 · see citing works
“17 Our study expanded on the previous evidence, identifying that subcortical localized inflammation is also associated with shorter survival in people with PSP.”
Self-citationDey, S., Yelamanchi, R., Mullapudi, T., Holla, V. V., Kamble, N. L., Mahale, R. R., Sathyaprabha, T. N., Pal, P. K., Debnath, M., & Yadav, R. (2024) · Annals of Indian Academy of Neurology · doi:10.4103/aian.aian_507_23 · Cited by 5 · see citing works
“[6] However, the high cost, invasive nature of the investigation, and non‑replicability of the findings among PSP variants restrict them from clinical translations.”
BackgroundScarpa, M., Vallera, E., Ausellé‐Bosch, S., Rocha, F. M., Mercan, B. E., Roy, A., Nordberg, A. K., & Kumar, A. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14409 · Cited by 5 · see citing works
Litvinenko, I., & Lobzin, V. Y. (2022) · Advances in Gerontology · doi:10.1134/s2079057022040117 · Cited by 5 · see citing works
“At the same time, the dynamics of structural changes, according to magnetic resonance imaging (MRI) data, does not correspond with the rate of disease development, in contrast to the intensity of progressive neuroinflammation [45].”
BackgroundPathomechanisms of neuropsychiatric disturbances in atypical parkinsonian disorders: a current view
Jellinger, K. A. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-02890-7 · Cited by 5 · see citing works
“Combined PET studies indexing microglial activation and tau pathology demonstrated that both co-localize in the same brain regions (Malpetti et al. 2021), enhancing a pathological cascade leading to dysfunction of essential neuronal circuitries.”
Comparing and combining TSPO-PET tracers in tauopathies
Crook, H., Franzmeier, N., Rahmouni, N., Gnörich, J. S., Fryer, T. D., Hong, Y. T., Roemer, S. N., Palleis, C., Strauss, A., Jones, P. S., et al. (2025) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-025-07579-3 · Cited by 5 · see citing works
“In neurodegenerative disease, TSPO has been shown to be upregulated in microglia [3-5], and to a lesser extent in astrocytes and vasculature.”
Self-citationDiagnostic utility of biomarkers in progressive supranuclear palsy: toward a biotyping framework
Ryan, C. B., Camargo, C. J., Salan, T., Pallikkuth, S., Gao, H., & Govind, V. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13539-6 · Cited by 4 · see citing works
“• Inflammatory biotype: characterized by high NLR (> 2.5), and 11 C-PK11195 PET uptake, this biotype reflects robust microglial activation and systemic inflammation [67, 108, 109].”
InfluentialMarkiewicz, M. G., Migda, B., Otto‐Ślusarczyk, D., Madetko‐Alster, N., Wiercińska‐Drapało, A., Darewicz, M., Struga, M., & Alster, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262412122 · Cited by 4 · see citing works
“Interestingly, tau accumulation and microglial activation were proven to be positively correlated with clinical course severity and were predictive factors for disease progression [11,12].”
Giordano, R., Canesi, M., Isalberti, M., Marfia, G., Campanella, R., Vincenti, D., Cereda, V., Ranghetti, A., Palmisano, C., Isaias, I. U., et al. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.723227 · Cited by 4 · see citing works
“Among other cell types, MSCs have dramatic antiinflammatory and immunomodulatory properties (Marigo and Dazzi, 2011).”
BackgroundNeurophysiological consequences of synapse loss in progressive supranuclear palsyPreprint
Adams, N., Jafarian, A., Perry, A., Rouse, M. A., Shaw, A. D., Murley, A. G., Cope, T., Bevan-Jones, W. R., Passamonti, L., Street, D., et al. (2022) · medRxiv · doi:10.1101/2022.06.22.22276697 · Cited by 4 · see citing works
Self-citationPET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects
Jin, H. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00338 · Cited by 4 · see citing works
Yadav, R., Dey, S., Kumar, R., Mohanan, A. P., Vasudevan, G. T., Harish, M., Kamble, N. L., Holla, V. V., Mahale, R. R., Mailankody, P., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0325624 · Cited by 3 · see citing works
“These were also evident in magnetic resonance imaging (MRI) and positron emission tomography (PET) which indicate the hegemony of pro-inflammatory cytokines in the central nervous system [20,21].”
Satoh, R., Utianski, R. L., Duffy, J. R., Clark, H. M., Stephens, Y. C., Lee, J., Baker, M. C., Rademakers, R., Lowe, V. J., Josephs, K. A., et al. (2025) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000005962 · Cited by 3 · see citing works
Phenotype parallels protein seeding capacity in neurodegenerative diseases
Martínez-Valbuena, I. (2024) · Brain Pathology · doi:10.1111/bpa.13238 · Cited by 3 · see citing works
“Interestingly, a recent study using positron emission tomography tracers that measure microglial activation and tau pathology in PSP patients, showed that neuroinflammation is key for progression of PSP [12] and our data would support this concept.”
BackgroundYamahara, N., Takekoshi, A., Kimura, A., & Shimohata, T. (2024) · Brain Sciences · doi:10.3390/brainsci14101012 · Cited by 3 · see citing works
“…recognized as an important aspect of PSP. Site and intensity of neuroinflammation were correlated with tau pathology [13] and clinical severity [14] on positron emission tomography; and cerebrospinal fluid (CSF) cytokines suggesting microglial activation including tumor necrosis factor alpha,…”
BackgroundKim, R., Kim, H. J., Lee, S., Jin, B., Kim, S., Ha, S. H., Choi, S., Shin, J. H., Kim, H.-J., Jeon, B., et al. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-03091-y · Cited by 1 · see citing works
“…(PET) imaging studies in PSP have shown that microglial activation occurs near neurofibrillary tangles and that this activation is associated with a greater tau pathology burden, more rapid clinical progression, and increased brain atrophy (Ishizawa and Dickson 2001; Malpetti et al. 2020, 2021 ).”
Neuroprotection trial design in progressive supranuclear palsy: challenges and solutions
Golbe, L. I., & Thomas, R. G. (2026) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70247 · Cited by 1 · see citing works
Jasak, P., Wesołowska, A., Żółtowska, M., Alster, P., & Madetko‐Alster, N. (2026) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2026.108917 · Cited by 1 · see citing works
The potential of proteomics for in-depth molecular investigations of progressive supranuclear palsy
Romero-Murillo, S., Lee, S., Fernández‐Irigoyen, J., Martínez-Valbuena, I., & Santamaría, E. (2025) · Expert Review of Proteomics · doi:10.1080/14789450.2025.2519466 · Cited by 1 · see citing works
“While extensive evidence in Alzheimer’s disease (AD) supports a link between tau misfolding and synaptic degeneration [21,22], the relationship in PSP remains less clear due to conflicting findings [23–26].”
Does increased microglial activation lead to faster progression in PSP?
Gerhard, A. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325980 · Cited by 1 · see citing works
Neuroimaging in progressive supranuclear palsy
de Natale, E. R., Wilson, H., Politis, M., & Niccolini, F. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821651-4.00004-x
(2023) · Advances in magnetic resonance technology and applications · doi:10.1016/b978-0-323-91771-1.00026-5
Neuroinflammation Imaging in Neurodegenerative Diseases
Hammoud, D. A., & Herscovitch, P. (2023) · Springer eBooks · doi:10.1007/978-3-031-35098-6_9
Lu, J., Ge, J., Yu, H., Zhao, G., & Chen, X. (2024) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000005062
Post-Mortem validation of in vivo 18kDa Translocator Protein (TSPO) PET as a microglial biomarkerPreprint
Wijesinghe, S. S., Rowe, J. B., Mason, H. D., Allinson, K. S. J., Thomas, R., Vontobel, D. S., Fryer, T. D., Hong, Y. T., Bacioglu, M., Spillantini, M. G., et al. (2024) · medRxiv · doi:10.1101/2024.07.15.24309178
“Microglia have gained particular interest as a dominant part of the central neuroinflammatory response, associated with disease severity and progression 2,3 .”
BackgroundSelf-citationGomez‐Virgilio, L., Gutierrez‐Malacara, A., Rivera‐Osorio, J., Silva‐Lucero, M., Padilla-Mendoza, J. R., Gómez-Ramírez, D. E., & Cárdenas-Aguayo, M. D. C. (2024) · Gaceta Médica de México · doi:10.24875/gmm.m24000930 · Cited by 1 · see citing works
Comparing and combining TSPO-PET tracers in tauopathiesPreprint
Crook, H., Franzmeier, N., Rahmouni, N., Gnörich, J. S., Fryer, T. D., Hong, Y. T., Roemer, S. N., Palleis, C., Strauss, A., Jones, P. S., et al. (2025) · medRxiv · doi:10.1101/2025.07.23.25332044
Self-citationShapiro, N. L., Jones, P. S., Mak, E., Tsvetanov, K. A., Goddard, J., Vontobel, D. S., Durcan, R., Chouliaras, L., Fryer, T. D., Hong, Y. T., et al. (2025) · medRxiv · doi:10.1101/2025.08.27.25334139
Self-citationDisease-specific tau polymorphs define unique protein interaction networks across proteinopathiesPreprint
Puangmalai, N., Bhatt, N. N., Suthprasertporn, N., Miranda-Morales, E. G., Shchankin, N., Samples, M., Balci, A. E., Liew, J. Y., Montalbano, M., Zhao, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.09.675096
Satoh, R., Ali, F., Dickson, D. W., Lowe, V. J., Josephs, K. A., & Whitwell, J. L. (2026) · Journal of Nuclear Medicine · doi:10.2967/jnumed.125.271019
Picillo, M., Basile, C., Montella, F., Lopardo, V., Orlando, M., Tarallo, R., Palumbo, D., Melone, V., Tepedino, M. F., Barone, P., et al. (2026) · Movement Disorders · doi:10.1002/mds.70273
Vontobel, D. S., Lai, K. O., Bacioglu, M., Nolan, G., Maddison, D. C., Adamski, A., Goddard, J., Shapiro, N. L., Crook, H., Fryer, T., et al. (2026) · medRxiv · doi:10.64898/2026.06.22.26356176
Self-citationVasoya, D., Keavey, L., Levit, C., Watzeels, T., Heron, S., Cholewa-Waclaw, J., Dando, O., Mancuso, R., & Bowles, K. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.30.735652 · Cited by 1 · see citing works
Harris, G. A., Barnhard, L., Brummet, J., & Diaz, K. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1893149
“Measuring both p-tau 181 and NfL in the CSF of PSP patients correlated with disease severity and rate of progression, and the ratio of NfL to p-tau was better at predicting changes in the PSPRS clinical rating scale, than either measure on its own (Rojas et al., 2018).”
InfluentialDisease-specific tau polymorphs are associated with unique protein networks across proteinopathies
Puangmalai, N., Bhatt, N. N., Suthprasertporn, N., Miranda-Morales, E. G., Shchankin, N., Samples, M., Balci, A. E., Liew, J. Y., Montalbano, M., Zhao, Y., et al. (2026) · The EMBO Journal · doi:10.1038/s44318-026-00897-8
“TRIM21 has been shown to neutralize cytosolic tau seeds by recruiting proteasomal and p97/VCP activity, offering a possible mechanistic interpretation for its PSP association in our dataset (Malpetti et al, 2021; Mukadam et al, 2023; Radford et al, 2023).”
Chen, X., Wang, X., Li, C., Shan, K., Wang, L., Hashimoto, K., Shao, K., Wei, P., & Yang, J.-J. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.106965 · Cited by 1 · see citing works
Migda, B., Kutyłowski, M., Madetko‐Alster, N., Migda, A. M., Kutyłowski, K., & Alster, P. (2026) · Neurology International · doi:10.3390/neurolint18090161
Magro, G., Laterza, V., Mechelli, A., Tosto, F., Longo, A., Camastra, C., & Quattrone, A. (2026) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2026.126162
Vontobel, D. S., Lai, K. O., Bacioglu, M., Nolan, G., Maddison, D. C., Adamski, A., Goddard, J., Shapiro, N. L., Crook, H., Fryer, T., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03103-5
“Increased TSPO binding in disease-specific regions predicts clinical decline, and correlates with tau pathology and its longitudinal progression [21, 22, 38].”
Self-citationThe characteristics of perivascular proinflammation in 4‐repeat tauopathies
Fu, M., Uruk, G., Gatto, R. G., Reichard, R. R., Whitwell, J. L., & Josephs, K. A. (2026) · Brain Pathology · doi:10.1111/bpa.70162
“Using both [ 11 C]PK11195 and [ 18 F]AV-1451 PET, the extent of neuroinflammation was correlated with the clinical manifestation and disease progression of AD and PSP [50, 51].”
- Authors
- Malpetti, M., Passamonti, L., Jones, P. S., Street, D., Rittman, T., Fryer, T. D., Hong, Y. T., Vàsquez Rodriguez, P., Bevan-Jones, W. R., Aigbirhio, F. I., O'Brien, J. T., & Rowe, J. B.
- Affiliations
- University of Cambridge (GB)
- National Academies of Sciences, Engineering, and Medicine (US)
- Corresponding author
- Rowe, James Benedict
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2021-03-17
- Volume
- 92
- Issue
- 7
- Pages
- 769-775
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- PMC
- PMC7611006
- OpenAlex
- W3136730170
- Cited by
- 85
- References
- 55
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 14 · 2023: 12 · 2022: 16 · 2021: 8 · 2020: 1
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- National Institute for Health Research Cambridge Biomedical Research Centre (146281)
- Cambridge Centre for Parkinson-Plus (RG95450)
- PSP Association (“MAPT-PSP” award)
- Medical Research Council (MR/P01271X/1)
- Wellcome Trust (103838)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- progressive supranuclear palsy, neuroinflammation, disease progression, prognostic imaging biomarkers, tau pathology, microglial activation, brainstem, cerebellum, gray matter volume, disease-modifying therapy, immunomodulatory therapy, patient stratification
- MeSH terms
- Aged, Brain, Encephalitis, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Severity of Illness Index, Supranuclear Palsy, Progressive, tau Proteins, Disease Progression, Positron-Emission Tomography
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