Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches
Open accessAbstract
Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases.
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Although the presence of an overt frontotemporal dementia syndrome can be defined on the basis of established criteria, there are no such criteria for the prodromal forms of frontotemporal lobar degeneration, except for progressive supranuclear palsy.
“Although the presence of an overt frontotemporal dementia syndrome can be defined on the basis of established criteria, there are no such criteria for the prodromal forms of fronto temporal lobar degeneration, except for progressive supranuclear See Online for appendix Review palsy.31”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [31]
Neuropathologically, PSP is defined by accumulation of pTau in both neurons and glial cells.
“Neuropathologically, PSP is defined by the accumulation of pTau in both neurons and glial cells.369”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [369]
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Clinical Approach to Progressive Supranuclear Palsy
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Progression of brain atrophy in PSP and CBS over 6 months and 1 year
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MRI measurements predict PSP in unclassifiable parkinsonisms
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Familial aggregation of parkinsonism in progressive supranuclear palsy
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Clinicopathological Outcomes of Prospectively Followed Normal Elderly Brain Bank Volunteers
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Retinal single-layer analysis in Parkinsonian syndromes: an optical coherence tomography study
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Molecular Genetics of Neurodegenerative DementiasPreprint
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Environmental and occupational risk factors for progressive supranuclear palsy: Case‐control study
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Self-citationCerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP‐C
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FDG-PET in pathologically confirmed spontaneous 4R-tauopathy variants
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A geographical cluster of progressive supranuclear palsy in northern France
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Self-citationFunctional MRI of disease progression in Parkinson disease and atypical parkinsonian syndromes
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CoQ10 in progressive supranuclear palsy
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Midbrain atrophy is not a biomarker of progressive supranuclear palsy pathology
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Rehabilitation in progressive supranuclear palsy: Effectiveness of two multidisciplinary treatments
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Diffusion tensor MRI contributes to differentiate Richardson's syndrome from PSP-parkinsonism
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Prevalence of progressive supranuclear palsy in Yonago: change throughout a decade
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Three sib-pairs of autopsy-confirmed progressive supranuclear palsy
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MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP–parkinsonism
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Peduncolopontine nucleus stimulation in progressive supranuclear palsy: a randomised trial
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Self-citationRest-activity rhythm disruption in progressive supranuclear palsy
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Self-citationThe clinical spectrum and natural history of pure akinesia with gait freezing
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Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria
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Self-citationMicroglia in neurodegenerative diseases: mechanism and potential therapeutic targets
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Self-citationAssessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy
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Self-citationEvolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies
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Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease
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Self-citationCSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP
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Clinical Utility of 18F‐APN ‐1607 Tau PET Imaging in Patients with Progressive Supranuclear Palsy
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CXCR4 involvement in neurodegenerative diseases
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Physiological changes in neurodegeneration—mechanistic insights and clinical utility
Ahmed, R. M., Ke, Y. D., Vucic, S., Ittner, L. M., Seeley, W., Hodges, J. R., Piguet, O., Halliday, G., & Kiernan, M. C. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2018.23 · Cited by 91 · see citing works
Gait and postural disorders in parkinsonism: a clinical approach
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Salivary alpha-synuclein in the diagnosis of Parkinson's disease and Progressive Supranuclear Palsy
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Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies
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Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients
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Self-citationThe therapeutic landscape of tauopathies: challenges and prospects
Cummings, J. L., González, M. I., Pritchard, M. C., May, P. C., Toledo, L. M., & Harris, G. A. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01321-7 · Cited by 80 · see citing works
Validation of the Movement Disorder Society Criteria for the Diagnosis of 4‐Repeat Tauopathies
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Self-citationA critical appraisal of tau‐targeting therapies for primary and secondary tauopathies
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Genetics of Progressive Supranuclear Palsy: A Review
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Characterization of tau binding by gosuranemab
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Clinical Aspects of the Differential Diagnosis of Parkinson’s Disease and Parkinsonism
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New classification of tauopathies
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MR planimetry in neurodegenerative parkinsonism yields high diagnostic accuracy for PSP
Mangesius, S., Hussl, A., Krismer, F., Mahlknecht, P., Reiter, E., Tagwercher, S., Djamshidian, A., Schocke, M. F. H., Esterhammer, R., Wenning, G. K., et al. (2017) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.10.020 · Cited by 57 · see citing works
Open‐Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy
VandeVrede, L. A., Dale, M. L., Fields, S., Frank, M., Hare, E. B., Heuer, H. W., Keith, K., KOESTLER, M. E., Ljubenkov, P. A., McDermott, D., et al. (2020) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12940 · Cited by 56 · see citing works
Self-citationThe Progressive Supranuclear Palsy Clinical Deficits Scale
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Self-citationSNMMI Procedure Standard/EANM Practice Guideline for Brain [ 18 F]FDG PET Imaging, Version 2.0
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Motor, cognitive and behavioral differences in MDS PSP phenotypes
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The ProNGF/p75NTR pathway induces tau pathology and is a therapeutic target for FTLD-tau
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Self-citationFour-Repeat Tauopathies: Current Management and Future Treatments
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Tau clearance improves astrocytic function and brain glutamate-glutamine cycle
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- Authors
- Boxer, A. L., Yu, J.-T., Golbe, L. I., Litvan, I., Lang, A. E., & Höglinger, G. U.
- Affiliations
- University of California, San Francisco (US)
- Qingdao University (CN)
- Rutgers, The State University of New Jersey (US)
- University of California San Diego (US)
- University of Toronto (CA)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Boxer, Adam L
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 16
- Issue
- 7
- Pages
- 552-563
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC5802400
- OpenAlex
- W2625168757
- Cited by
- 485
- References
- 105
- Citations by year
- 2026: 45 · 2025: 52 · 2024: 59 · 2023: 42 · 2022: 57 · 2021: 56 · 2020: 62 · 2019: 61 · 2018: 43 · 2017: 7
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (HO2402/6‐2)
- National Institutes of Health
- National Institute on Aging (P50AG005131, U01AG045390, R01AG038791, P01AG019724)
- National Heart, Lung, and Blood Institute (T35HL007491)
- National Institute of Neurological Disorders and Stroke (U01NS086659, U54NS092089)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- progressive supranuclear palsy, diagnostic criteria, tau pathology, 4-repeat tau, biomarkers, atypical parkinsonism, disease-modifying therapy, neurodegenerative diseases, Alzheimer's disease, chronic traumatic encephalopathy
- MeSH terms
- Humans, Supranuclear Palsy, Progressive, Biomarkers
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