Progressive Supranuclear Palsy

1. Disease Information

1.1 Definition and overview

Progressive supranuclear palsy (PSP) is a neuropathologically defined, adult-onset, rapidly progressive neurodegenerative disorder in which abnormal tau aggregates (predominantly 4-repeat/4R tau) accumulate in neurons and glia, producing characteristic motor (postural instability, falls, akinesia), ocular motor, and cognitive/behavioral syndromes. Definite diagnosis remains neuropathologic, but research/clinical criteria have been revised to improve ante-mortem sensitivity for variant phenotypes. (hoglinger2017clinicaldiagnosisof pages 2-3, wise2024csfproteomicsin pages 1-2, whitney2024singlecelltranscriptomicand pages 1-2)

A widely recognized “classical” clinical phenotype is PSP–Richardson syndrome (PSP-RS), often featuring oculomotor dysfunction and early postural instability, with median survival reported as ~6.9 years in a contemporary biomarker cohort study. (wise2024csfproteomicsin pages 1-2)

1.2 Key identifiers and synonyms

A MONDO disease identifier is available via OpenTargets: MONDO:0019037 (progressive supranuclear palsy). (OpenTargets Search: Progressive supranuclear palsy)

ICD coding in retrieved sources: ICD-9 333.0 was used for case ascertainment in an Israeli health-provider cohort; authors noted nonspecificity requiring verification for externally coded diagnoses. ICD-10, MeSH, and OMIM numeric identifiers were not explicitly provided in the retrieved texts. (barer2023progressivesupranuclearpalsy’s pages 1-2)

Common synonyms/clinical labels include PSP-RS, PSP-P (parkinsonism), PSP-PGF (progressive gait freezing), PSP-SL (speech/language), PSP-F (frontal/behavioral), PSP-CBS, PSP-OM, PSP-PI, and others per MDS framework. (hoglinger2017clinicaldiagnosisof pages 3-4, nasri2024phenotypicspectrumof pages 1-2)

Table: This table compiles key standardized identifiers and commonly used clinical synonyms/phenotype labels for progressive supranuclear palsy. It is useful for mapping disease terminology across ontologies, coding systems, and clinical subtype literature.

1.3 Evidence source type (patient-level vs aggregated)

PSP characterization is derived from both aggregated resources (e.g., OpenTargets ontology mapping) and aggregated cohort/trial/omics literature. Real-world evidence in this report includes retrospective medical-record abstraction across multiple care centers in the US/Canada and a large Israeli payer-provider database cohort. (nysetvold2024progressivesupranuclearpalsy pages 1-2, barer2023progressivesupranuclearpalsy’s pages 1-2)

2. Etiology

2.1 Primary causal factors

PSP is typically sporadic, with pathogenesis centered on tau (MAPT) biology, especially 4R tau accumulation and aggregation in vulnerable brain regions and cell types. (hoglinger2017clinicaldiagnosisof pages 2-3, whitney2024singlecelltranscriptomicand pages 1-2)

Rare familial PSP-like syndromes can occur with MAPT mutations, but most cases lack Mendelian inheritance; in MDS criteria, MAPT mutations are not an exclusion criterion but define inherited vs sporadic PSP. (hoglinger2017clinicaldiagnosisof pages 3-4)

2.2 Genetic risk factors (2023–2024 emphasis)

A 2024 whole-genome sequencing (WGS) case-control study (European ancestry) emphasized that prior array-GWAS were limited for rare variants and structural variants (SVs), and used WGS to analyze SNVs/indels/SVs at scale. (wang2024wholegenomesequencinganalysis pages 1-2)

Key genetic findings include: - MAPT 17q21.31 H1 haplotype is the strongest known common risk factor; the WGS study reports an estimated OR = 5.6 for H1 carriers. (wang2024wholegenomesequencinganalysis pages 1-2) - WGS confirmed known loci (e.g., MAPT, MOBP, STX6, SLCO1A2, DUSP10, SP1) and identified novel common signals (APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, ELOVL1). (wang2024wholegenomesequencinganalysis pages 1-2) - Notably, APOE ε2 was observed as the risk allele in PSP (in contrast to Alzheimer’s disease). (wang2024wholegenomesequencinganalysis pages 1-2) - Rare-variant association implicated ZNF592, and SV associations included seven common SVs in 17q21.31 and other loci (IGH, PCMT1, CYP2A13, SMCP), plus a burden of rare deletions/duplications in 17q21.31 (P = 6.73 × 10^-3). (wang2024wholegenomesequencinganalysis pages 1-2)

Mechanistically, MAPT haplotype effects are supported by transcriptomic evidence: a 2024 post-mortem bulk RNA-seq study found increased total tau mRNA and increased proportion of 4R transcripts in PSP brain regions, with 4R tau mRNA levels associated with the H1 haplotype, consistent with a causal role for altered splicing/expression. (ressler2024mapthaplotypeassociatedtranscriptomic pages 1-2)

Table: This table summarizes the main genetic risk factors and loci implicated in progressive supranuclear palsy, emphasizing the 2024 WGS study and related transcriptomic evidence. It is useful for quickly mapping confirmed loci, novel signals, structural variation findings, and effect estimates such as the MAPT H1 haplotype odds ratio.

2.3 Environmental risk/protective factors and gene–environment interactions

No high-quality, PSP-specific environmental risk factors, protective factors, or gene–environment interactions were identified within the retrieved evidence set for this run. This should be treated as insufficient evidence in the current retrieval, not as evidence of absence.

3. Phenotypes

3.1 Core clinical domains and spectrum

The 2017 MDS-PSP criteria identify four functional domains as clinical predictors: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, with features contributing different diagnostic certainty levels (probable, possible, suggestive). (hoglinger2017clinicaldiagnosisof pages 2-3)

Variant clinical presentations beyond PSP-RS are common in autopsy series, motivating the criteria revision. (hoglinger2017clinicaldiagnosisof pages 2-3)

3.2 Phenotype frequencies and timelines (recent cohort evidence)

• In a 2024 Tunisian cohort recategorized by MDS-PSP phenotypes (n=112), the distribution included PSP-RS (48), PSP-cortical (34; e.g., PSP-CBS 17.6%, PSP-F 9.4%, PSP-SL 8.2%), and PSP-subcortical (30; PSP-P 11.6%, PSP-PI 8.0%, PSP-OM 2.7%, PSP-PGF 1.8%, PSP-C 1.8%, PSP-PLS 0.9%). (nasri2024phenotypicspectrumof pages 1-2)
• In a 2024 US/Canada medical-record real-world study (n=72), falls were documented in 79.2% before diagnosis and 97.2% during the course; among those with onset dates documented, median onset was 2.0 years before diagnosis for first fall, 1.2 years for unsteady gait/gait impairment, and 0.8 years for mobility problems. (nysetvold2024progressivesupranuclearpalsy pages 1-2, nysetvold2024progressivesupranuclearpalsy pages 2-4)

3.3 HPO term suggestions

A practical mapping of major PSP symptoms to HPO labels is provided below.

Table: This table maps common progressive supranuclear palsy phenotypes and core symptoms to suggested HPO terms, while adding quantitative cohort data where available. It is useful for phenotype annotation in a disease knowledge base and for harmonizing clinical features across PSP subtypes.

3.4 Quality of life impact

Direct QoL instrument data (e.g., EQ-5D, SF-36) were not extracted from the retrieved primary evidence in this run; however, real-world evidence indicates extensive supportive-care and assistive-device needs (see Treatments/Applications section), which reflect substantial functional impairment burden. (nysetvold2024progressivesupranuclearpalsy pages 1-2)

4. Genetic/Molecular Information

4.1 Major genes and loci

Key genes/loci supported by contemporary WGS and/or prior GWAS replication include MAPT, MOBP, STX6, SLCO1A2, DUSP10, SP1, with novel signals including APOE and others. (wang2024wholegenomesequencinganalysis pages 1-2)

4.2 Pathogenic variants (rare familial PSP and related syndromes)

The retrieved MDS criteria explicitly note that MAPT rare variants (mutations) are not an exclusion criterion but indicate inherited PSP; MDS criteria also note that MAPT H2 homozygosity is not an exclusion but makes PSP less likely. (hoglinger2017clinicaldiagnosisof pages 3-4)

A complete ClinVar/gnomAD-level catalog (variant nomenclature and allele frequencies) was not obtained in this run.

4.3 Epigenetic information

An epigenome-wide DNA methylation comparison in frontal lobe white matter across parkinsonian disorders identified shared and disease-relevant pathway dysregulation including Wnt signaling, ER stress, mitochondrial processes, RNA interference, and endosomal transport. (murthy2024dnamethylationpatterns pages 1-2)

5. Environmental Information

No PSP-specific infectious/toxic/lifestyle drivers were identified within the retrieved sources for this run. Gastrointestinal dysfunction is frequent in PSP and is being therapeutically targeted (FMT trial), but this does not establish a causal environmental etiology. (tian2023efficacyoffaecal pages 1-2)

6. Mechanism / Pathophysiology (Current Understanding, 2023–2024 emphasis)

6.1 Causal chain (high-level)

Genetic predisposition (notably MAPT H1 haplotype and additional risk loci including stress-pathway genes such as EIF2AK3/PERK) appears to bias tau expression/splicing toward 4R isoforms. This supports a cellular environment prone to tau misfolding/aggregation and spread. Subsequent downstream cascades include ER stress/integrated stress response activation, synaptic/axon guidance and trafficking pathway dysregulation, and neuroinflammatory activation, culminating in region- and cell-type-specific degeneration and clinical syndromes. (wang2024wholegenomesequencinganalysis pages 1-2, ressler2024mapthaplotypeassociatedtranscriptomic pages 1-2, whitney2024singlecelltranscriptomicand pages 1-2, wise2024csfproteomicsin pages 1-2)

6.2 Cell types, pathways, and regions (ontology-ready)

A structured mechanism table with CL/GO/UBERON suggestions is provided.

Table: This table summarizes major molecular and cellular mechanisms implicated in progressive supranuclear palsy, linking genetic risk, tau biology, stress signaling, white-matter epigenetics, and neuroinflammation to vulnerable cell types and brain regions. It is useful for knowledge-base annotation because it also suggests ontology terms for cells, anatomy, and biological processes.

Key recent mechanistic developments include: - Single-nucleus RNA-seq (50,708 nuclei) in PSP diencephalon demonstrated EIF2 signaling activation across vulnerable cell types; activated eIF2α correlated with tau burden and localized to p-tau+ neurons and ALDH1L1+ astrocytes by multiplex imaging, supporting integrated stress response failure as a mechanistic component. (whitney2024singlecelltranscriptomicand pages 1-2, whitney2024singlecelltranscriptomicand pages 12-14) - CSF proteomics (SomaScan) identified convergent downregulation of axon guidance and other modules (synaptic/JAK-STAT, vesicle-cytoskeletal trafficking, cytokine signaling) with high AUC discrimination panels, implicating circuit-level dysfunction consistent with axonal/synaptic pathology. (wise2024csfproteomicsin pages 1-2) - A MAPT expression study using RNAscope + AT8 and snRNA-seq found MAPT transcripts in neurons, astrocytes, and oligodendrocytes and preserved expression in cells with tau aggregates, supporting ongoing local tau supply for aggregation/seeding and motivating dual therapeutic approaches. (forrest2023cellspecificmaptgene pages 1-2)

7. Anatomical Structures Affected

PSP pathology and biomarker studies emphasize subcortical and brainstem structures with additional cortical involvement depending on phenotype. Key regions include the subthalamic nucleus, globus pallidus, dorsal midbrain, and cerebellar/diencephalic structures, with clinical variants reflecting differing neuroanatomic distributions of pathology. (wise2024csfproteomicsin pages 1-2, whitney2024singlecelltranscriptomicand pages 1-2)

Cell types prominently implicated include neurons, astrocytes, and oligodendrocytes, consistent across neuropathology, transcriptomics, and genetic findings highlighting oligodendrocyte/myelin biology. (whitney2024singlecelltranscriptomicand pages 1-2, wang2024wholegenomesequencinganalysis pages 1-2)

8. Temporal Development

PSP typically begins after age 60 in many series, with diagnosis often delayed due to early symptom overlap with Parkinson’s disease and other atypical parkinsonisms. (jang2024biomarkerdiscoveryin pages 1-2, hoglinger2017clinicaldiagnosisof pages 2-3)

Real-world data show a multi-year prodrome before diagnosis, with falls and gait impairment commonly preceding formal diagnosis by ~1–2 years (median values among those with onset dates documented). (nysetvold2024progressivesupranuclearpalsy pages 1-2)

9. Inheritance and Population

9.1 Epidemiology

Recent biomarker and review sources report PSP-RS prevalence in the 2.3–10.6 per 100,000 range, with broader PSP prevalence estimates up to ~18 per 100,000 in some population studies. (wise2024csfproteomicsin pages 1-2, boxer2017advancesinprogressive pages 1-2)

9.2 Inheritance

PSP is predominantly sporadic, with rare familial MAPT mutation-associated PSP-like syndromes. MDS criteria incorporate genetic findings into exclusion/context decisions and distinguish inherited vs sporadic PSP when MAPT mutations are present. (hoglinger2017clinicaldiagnosisof pages 3-4, whitney2024singlecelltranscriptomicand pages 1-2)

9.3 Prognosis and natural history

• Median survival estimates include ~6.9 years in PSP-RS (biomarker cohort) and median 7.3 years after symptom onset in the gosuranemab PASSPORT trial report. (wise2024csfproteomicsin pages 1-2, dam2021safetyandefficacy pages 1-6)
• In a representative UK cohort (n=227), survival was longer in variant phenotypes than Richardson’s syndrome (7.3 vs 5.6 years, P=0.02), and annual cognitive decline differed by phenotype (MMSE -1.8 vs -0.9/year; ACE-R -5.3 vs -3.0/year). (street2021clinicalprogressionof pages 1-2)

10. Diagnostics

10.1 Clinical criteria (authoritative)

The 2017 Movement Disorder Society (MDS) criteria were developed to improve early and variant-phenotype sensitivity relative to NINDS-SPSP criteria, while maintaining specificity. They incorporate mandatory inclusion/exclusion criteria and define diagnostic certainty categories (probable, possible, suggestive) based on combinations of features across four functional domains. (hoglinger2017clinicaldiagnosisof pages 2-3)

Key excerpted features include: - NINDS-SPSP “probable” PSP requires vertical supranuclear gaze palsy plus postural instability and falls within 1 year, but sensitivity is limited early and for variants. (hoglinger2017clinicaldiagnosisof pages 2-3) - MDS-PSP criteria incorporate imaging/laboratory/genetic context; for example, in PSP-CBS, CSF constellations typical of AD (elevated total/p-tau plus reduced Aβ42) or amyloid PET are used to exclude primary AD pathology. (hoglinger2017clinicaldiagnosisof pages 3-4)

10.2 Biomarkers and imaging (2024 priority)

A structured biomarker summary is provided below.

Table: This table summarizes key fluid and imaging biomarkers for progressive supranuclear palsy, including diagnostic and prognostic use cases, quantitative findings, and source citations. It is useful for comparing emerging 2024 proteomic and tau-PET markers with established MRI and CSF indicators.

Highlights include: - CSF mass-spectrometry proteomics identified ATP6AP2 as a strong discriminator (AUC 0.922) and enriched pathways (cell adhesion, cholesterol metabolism, glycan biosynthesis). (jang2024biomarkerdiscoveryin pages 1-2) - SomaScan CSF proteomics identified axon-guidance pathway protein panels with AUC up to 0.932 and inflammatory correlates of severity. (wise2024csfproteomicsin pages 1-2) - 18F-PI-2620 tau PET was associated with fluid biomarker ratios and cognition/atrophy in probable PSP-RS (preprint evidence). (dilcher2024linkingpi2620taupet pages 1-5)

11. Outcome / Prognosis

PSP has rapid progression with substantial disability burden and limited disease-modifying options; survival is typically on the order of 5–8 years from symptom onset depending on phenotype and cohort. (dam2021safetyandefficacy pages 1-6, street2021clinicalprogressionof pages 1-2)

Real-world studies show high healthcare utilization, including near-universal medication and imaging use, high assistive-device and supportive-care use, and increasing costs over time. (nysetvold2024progressivesupranuclearpalsy pages 1-2, barer2023progressivesupranuclearpalsy’s pages 1-2)

12. Treatment

12.1 Symptomatic and supportive care (real-world implementation)

Real-world care pathways rely heavily on symptomatic management and supportive services. In a US/Canada medical-record cohort, the most widely used resources (≥85% of participants at some point) were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries/procedures (85%). (nysetvold2024progressivesupranuclearpalsy pages 1-2)

In an Israeli payer-provider cohort, symptomatic therapies listed include levodopa/dopamine agonists/amantadine for motor symptoms (often mild/transient benefit), sleep and ocular symptom treatments, constipation management, antidepressants, and botulinum toxin for selected dystonia/sialorrhea syndromes; multidisciplinary therapy (physical, speech, occupational, social work) is emphasized. (barer2023progressivesupranuclearpalsy’s pages 1-2)

Suggested MAXO terms (labels): monoclonal antibody therapy; fecal microbiota transplantation; physical therapy; speech therapy; occupational therapy; assistive device use; supportive care.

12.2 Disease-modifying and experimental therapies (trials)

A consolidated trial table (including pipeline trials) is provided.

Table: This table summarizes interventional PSP studies with reported outcomes, active pipeline trials from retrieved ClinicalTrials.gov results, and real-world management/cost studies. It is useful for quickly comparing therapeutic classes, trial status, quantitative efficacy signals, and care burden.

Key completed disease-modifying trial outcomes: - Gosuranemab (NCT03068468): no clinical benefit (PSPRS change 10.4 vs 10.6 at week 52; P=0.85) despite strong CSF N-terminal tau target engagement (-98%). (dam2021safetyandefficacy pages 1-6) - Tilavonemab/ABBV-8E12 (NCT02985879): terminated for futility; no PSPRS benefit at week 52 vs placebo. (hoglinger2021safetyandefficacy pages 1-2)

Notable 2023–2024 development: - FMT in PSP-RS (ChiCTR-2100045397): phase 2 single-center trial showed improvement in PSPRS at week 16 and sustained nonmotor symptom improvements, providing a provocative but as-yet single-center signal requiring replication. (tian2023efficacyoffaecal pages 1-2)

13. Prevention

No primary prevention or proven protective factors were identified in the retrieved evidence set. Current best-supported “prevention” is tertiary: reducing falls and aspiration risk, managing dysphagia/constipation/mood symptoms, and implementing assistive devices and supportive therapies early. (nysetvold2024progressivesupranuclearpalsy pages 1-2, barer2023progressivesupranuclearpalsy’s pages 1-2)

Earlier detection is being advanced via MDS criteria adoption and emerging biomarkers (CSF proteomic panels, tau PET, NfL-based staging/prognosis). (hoglinger2017clinicaldiagnosisof pages 2-3, wise2024csfproteomicsin pages 1-2)

14. Other Species / Natural Disease

No naturally occurring PSP-equivalent disease in non-human species was identified in the retrieved sources for this run.

15. Model Organisms and Experimental Models (2023–2024)

A major current limitation is that conventional iPSC-derived neurons express low 4R tau, hindering modeling of 4R tauopathies such as PSP. A 2024 Cell study reports engineered hiPSC-derived neuronal lines expressing 4R tau (and 4R P301S) that develop progressive tau inclusions after seeding and enable CRISPRi screens identifying modifiers of tau propagation, supporting human-relevant target discovery platforms. (bravo2024humanipsc4r pages 1-3)

Human tissue-based mechanistic mapping supports glial involvement: MAPT transcripts were detected and preserved in neurons, astrocytes, and oligodendrocytes with tau aggregates in PSP, motivating combined approaches (reduce MAPT expression plus remove misfolded tau). (forrest2023cellspecificmaptgene pages 1-2)

Expert opinion / analysis (authoritative synthesis)

Two overarching themes emerge from authoritative and recent sources: 1) PSP is best conceptualized as a spectrum of clinical phenotypes underpinned by a shared 4R tau neuropathology; therefore, diagnostic frameworks and biomarkers must capture early and variant presentations rather than only PSP-RS. This is the central rationale of the 2017 MDS criteria revision. (hoglinger2017clinicaldiagnosisof pages 2-3, boxer2017advancesinprogressive pages 1-2) 2) The lack of clinical efficacy in anti-tau antibody trials despite strong CSF target engagement implies that either the targeted tau species/compartment is not causally dominant, the intervention timing is too late, or pharmacology does not adequately address intracellular pathology and downstream stress/inflammatory cascades. This motivates: (i) better pharmacodynamic and disease-biology biomarkers, and (ii) multi-target approaches addressing upstream splicing/expression (MAPT), intracellular proteostasis/ISR, and neuroimmune pathways. (dam2021safetyandefficacy pages 1-6, whitney2024singlecelltranscriptomicand pages 1-2, wise2024csfproteomicsin pages 1-2)

Key statistics (recent and high-value)

• Prevalence: PSP-RS 2.3–10.6 per 100,000 (wise2024csfproteomicsin pages 1-2); broader PSP up to ~18 per 100,000 in some studies (boxer2017advancesinprogressive pages 1-2).
• Survival: PSP-RS median survival 6.9 years (wise2024csfproteomicsin pages 1-2); death within median 7.3 years after symptom onset in PASSPORT report (dam2021safetyandefficacy pages 1-6).
• Real-world prediagnosis timing: first fall median 2.0 years before diagnosis; gait impairment 1.2 years; mobility problems 0.8 years (nysetvold2024progressivesupranuclearpalsy pages 1-2).
• Genetics: MAPT H1 haplotype OR ~5.6 (wang2024wholegenomesequencinganalysis pages 1-2); SV burden P=6.73×10^-3 (wang2024wholegenomesequencinganalysis pages 1-2).
• Biomarkers: ATP6AP2 AUC 0.922 in CSF proteomics (jang2024biomarkerdiscoveryin pages 1-2); axon-guidance CSF panel AUC up to 0.932 (wise2024csfproteomicsin pages 1-2).
• Trial outcomes: gosuranemab PSPRS 10.4 vs 10.6 at 52 weeks, P=0.85, with CSF N-term tau -98% (dam2021safetyandefficacy pages 1-6); tilavonemab no PSPRS benefit (hoglinger2021safetyandefficacy pages 1-2); FMT benefit 4.3 PSPRS points at week 16 (tian2023efficacyoffaecal pages 1-2).
• Healthcare costs: annual direct costs rose to US$21,637 at year 5 and US$36,693 at year 10 vs US$8,910 pre-diagnosis (barer2023progressivesupranuclearpalsy’s pages 1-2).

Limitations of this report (data availability)

• OMIM, MeSH, ICD-10, and Orphanet numeric identifiers were not explicitly retrievable in the provided texts beyond MONDO and Orphanet subtype labels surfaced via OpenTargets.
• Variant-level details (ClinVar classifications, allele frequencies) and PSP-specific environmental risk/protective factors were not captured in this retrieval.
• Some biomarker and imaging findings (e.g., PI-2620 tau PET linkage) were available as preprint evidence.

References

1. (hoglinger2017clinicaldiagnosisof pages 2-3): Günter U. Höglinger, Gesine Respondek, Maria Stamelou, Carolin Kurz, Keith A. Josephs, Anthony E. Lang, Brit Mollenhauer, Ulrich Müller, Christer Nilsson, Jennifer L. Whitwell, Thomas Arzberger, Elisabet Englund, Ellen Gelpi, Armin Giese, David J. Irwin, Wassilios G. Meissner, Alexander Pantelyat, Alex Rajput, John C. van Swieten, Claire Troakes, Angelo Antonini, Kailash P. Bhatia, Yvette Bordelon, Yaroslau Compta, Jean-Christophe Corvol, Carlo Colosimo, Dennis W. Dickson, Richard Dodel, Leslie Ferguson, Murray Grossman, Jan Kassubek, Florian Krismer, Johannes Levin, Stefan Lorenzl, Huw R. Morris, Peter Nestor, Wolfgang H. Oertel, Werner Poewe, Gil Rabinovici, James B. Rowe, Gerard D. Schellenberg, Klaus Seppi, Thilo van Eimeren, Gregor K. Wenning, Adam L. Boxer, Lawrence I. Golbe, and Irene Litvan. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Movement Disorders, 32:853-864, Jun 2017. URL: https://doi.org/10.1002/mds.26987, doi:10.1002/mds.26987. This article has 2649 citations and is from a highest quality peer-reviewed journal.

2. (wise2024csfproteomicsin pages 1-2): Amy Wise, Jingyao Li, Mai Yamakawa, Joseph Loureiro, Brant Peterson, Kathleen Worringer, Rajeev Sivasankaran, Jose-Alberto Palma, Laura Mitic, Hilary W. Heuer, Argentina Lario-Lago, Adam M. Staffaroni, Annie Clark, Jack Taylor, Peter A. Ljubenkov, Lawren Vandevrede, Lea T. Grinberg, Salvatore Spina, William W. Seeley, Bruce L. Miller, Bradley F. Boeve, Bradford C. Dickerson, Murray Grossman, Irene Litvan, Alexander Pantelyat, Maria Carmela Tartaglia, Zihan Zhang, Anne-Marie A. Wills, Jessica Rexach, Julio C. Rojas, and Adam L. Boxer. Csf proteomics in patients with progressive supranuclear palsy. Neurology, Aug 2024. URL: https://doi.org/10.1212/wnl.0000000000209585, doi:10.1212/wnl.0000000000209585. This article has 15 citations and is from a highest quality peer-reviewed journal.

3. (whitney2024singlecelltranscriptomicand pages 1-2): Kristen Whitney, Won-Min Song, Abhijeet Sharma, Diana K. Dangoor, Kurt Farrell, Margaret M. Krassner, Hadley W. Ressler, Thomas D. Christie, Shrishtee Kandoi, Ruth H. Walker, Melissa J. Nirenberg, Steven J. Frucht, Giulietta M. Riboldi, Bin Zhang, Ana C. Pereira, and John F. Crary. Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy. Acta Neuropathologica, Dec 2024. URL: https://doi.org/10.1007/s00401-024-02823-w, doi:10.1007/s00401-024-02823-w. This article has 15 citations and is from a highest quality peer-reviewed journal.

4. (OpenTargets Search: Progressive supranuclear palsy): Open Targets Query (Progressive supranuclear palsy, 9 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

5. (barer2023progressivesupranuclearpalsy’s pages 1-2): Yael Barer, Raanan Cohen, Meital Grabarnik-John, Xiaolan Ye, Jorge Zamudio, Tanya Gurevich, and Gabriel Chodick. Progressive supranuclear palsy’s economical burden: the use and costs of healthcare resources in a large health provider in israel. Journal of Neurology, 270:3770-3778, Apr 2023. URL: https://doi.org/10.1007/s00415-023-11714-1, doi:10.1007/s00415-023-11714-1. This article has 2 citations and is from a domain leading peer-reviewed journal.

6. (hoglinger2017clinicaldiagnosisof pages 3-4): Günter U. Höglinger, Gesine Respondek, Maria Stamelou, Carolin Kurz, Keith A. Josephs, Anthony E. Lang, Brit Mollenhauer, Ulrich Müller, Christer Nilsson, Jennifer L. Whitwell, Thomas Arzberger, Elisabet Englund, Ellen Gelpi, Armin Giese, David J. Irwin, Wassilios G. Meissner, Alexander Pantelyat, Alex Rajput, John C. van Swieten, Claire Troakes, Angelo Antonini, Kailash P. Bhatia, Yvette Bordelon, Yaroslau Compta, Jean-Christophe Corvol, Carlo Colosimo, Dennis W. Dickson, Richard Dodel, Leslie Ferguson, Murray Grossman, Jan Kassubek, Florian Krismer, Johannes Levin, Stefan Lorenzl, Huw R. Morris, Peter Nestor, Wolfgang H. Oertel, Werner Poewe, Gil Rabinovici, James B. Rowe, Gerard D. Schellenberg, Klaus Seppi, Thilo van Eimeren, Gregor K. Wenning, Adam L. Boxer, Lawrence I. Golbe, and Irene Litvan. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Movement Disorders, 32:853-864, Jun 2017. URL: https://doi.org/10.1002/mds.26987, doi:10.1002/mds.26987. This article has 2649 citations and is from a highest quality peer-reviewed journal.

7. (nasri2024phenotypicspectrumof pages 1-2): Amina Nasri, Ikram Sghaier, Anis Neji, Alya Gharbi, Youssef Abida, Saloua Mrabet, Amina Gargouri, Mouna Ben Djebara, Imen Kacem, and Riadh Gouider. Phenotypic spectrum of progressive supranuclear palsy: clinical study and apolipoprotein e effect. Journal of Movement Disorders, 17:158-170, Apr 2024. URL: https://doi.org/10.14802/jmd.23178, doi:10.14802/jmd.23178. This article has 13 citations and is from a peer-reviewed journal.

8. (boxer2017advancesinprogressive pages 3-4): Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, and Günter U Höglinger. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Jul 2017. URL: https://doi.org/10.1016/s1474-4422(17)30157-6, doi:10.1016/s1474-4422(17)30157-6. This article has 515 citations and is from a highest quality peer-reviewed journal.

9. (nysetvold2024progressivesupranuclearpalsy pages 1-2): Ella Nysetvold, Lauren N. Lopez, Ashley N. Cogell, Henrik Fryk, Nelson D. Pace, Sara Snell Taylor, Joyce Rhoden, Caitlin A. Nichols, Demetris Pillas, Alexander Klein, Teresa Gasalla, and Anna Scowcroft. Progressive supranuclear palsy (psp) disease progression, management, and healthcare resource utilization: a retrospective observational study in the us and canada. Orphanet Journal of Rare Diseases, May 2024. URL: https://doi.org/10.1186/s13023-024-03168-z, doi:10.1186/s13023-024-03168-z. This article has 9 citations and is from a peer-reviewed journal.

10. (wang2024wholegenomesequencinganalysis pages 1-2): Hui Wang, Timothy S. Chang, Beth A. Dombroski, Po-Liang Cheng, Vishakha Patil, Leopoldo Valiente-Banuet, Kurt Farrell, Catriona Mclean, Laura Molina-Porcel, Alex Rajput, Peter Paul De Deyn, Nathalie Le Bastard, Marla Gearing, Laura Donker Kaat, John C. Van Swieten, Elise Dopper, Bernardino F. Ghetti, Kathy L. Newell, Claire Troakes, Justo G. de Yébenes, Alberto Rábano-Gutierrez, Tina Meller, Wolfgang H. Oertel, Gesine Respondek, Maria Stamelou, Thomas Arzberger, Sigrun Roeber, Ulrich Müller, Franziska Hopfner, Pau Pastor, Alexis Brice, Alexandra Durr, Isabelle Le Ber, Thomas G. Beach, Geidy E. Serrano, Lili-Naz Hazrati, Irene Litvan, Rosa Rademakers, Owen A. Ross, Douglas Galasko, Adam L. Boxer, Bruce L. Miller, Willian W. Seeley, Vivanna M. Van Deerlin, Edward B. Lee, Charles L. White, Huw Morris, Rohan de Silva, John F. Crary, Alison M. Goate, Jeffrey S. Friedman, Yuk Yee Leung, Giovanni Coppola, Adam C. Naj, Li-San Wang, Clifton Dalgard, Dennis W. Dickson, Günter U. Höglinger, Gerard D. Schellenberg, Daniel H. Geschwind, and Wan-Ping Lee. Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy. Molecular Neurodegeneration, Aug 2024. URL: https://doi.org/10.1186/s13024-024-00747-3, doi:10.1186/s13024-024-00747-3. This article has 38 citations and is from a highest quality peer-reviewed journal.

11. (ressler2024mapthaplotypeassociatedtranscriptomic pages 1-2): Hadley W. Ressler, Jack Humphrey, Ricardo A. Vialle, Bergan Babrowicz, Shrishtee Kandoi, Towfique Raj, Dennis W. Dickson, Nilüfer Ertekin-Taner, John F. Crary, and Kurt Farrell. Mapt haplotype-associated transcriptomic changes in progressive supranuclear palsy. Acta Neuropathologica Communications, Aug 2024. URL: https://doi.org/10.1186/s40478-024-01839-3, doi:10.1186/s40478-024-01839-3. This article has 12 citations and is from a peer-reviewed journal.

12. (dunning2024pharmacotherapiesforthe pages 3-4): Elise E. Dunning, Boris Decourt, Nasser H. Zawia, Holly A. Shill, and Marwan N. Sabbagh. Pharmacotherapies for the treatment of progressive supranuclear palsy: a narrative review. Neurology and Therapy, 13:975-1013, May 2024. URL: https://doi.org/10.1007/s40120-024-00614-9, doi:10.1007/s40120-024-00614-9. This article has 9 citations and is from a domain leading peer-reviewed journal.

13. (nysetvold2024progressivesupranuclearpalsy pages 2-4): Ella Nysetvold, Lauren N. Lopez, Ashley N. Cogell, Henrik Fryk, Nelson D. Pace, Sara Snell Taylor, Joyce Rhoden, Caitlin A. Nichols, Demetris Pillas, Alexander Klein, Teresa Gasalla, and Anna Scowcroft. Progressive supranuclear palsy (psp) disease progression, management, and healthcare resource utilization: a retrospective observational study in the us and canada. Orphanet Journal of Rare Diseases, May 2024. URL: https://doi.org/10.1186/s13023-024-03168-z, doi:10.1186/s13023-024-03168-z. This article has 9 citations and is from a peer-reviewed journal.

14. (dam2021safetyandefficacy pages 1-6): Tien Dam, Adam L. Boxer, Lawrence I. Golbe, Günter U. Höglinger, Huw R. Morris, Irene Litvan, Anthony E. Lang, Jean-Christophe Corvol, Ikuko Aiba, Michael Grundman, Lili Yang, Beth Tidemann-Miller, Joseph Kupferman, Kristine Harper, Kubra Kamisoglu, Michael J. Wald, Danielle L. Graham, Liz Gedney, John O’Gorman, and Samantha Budd Haeberlein. Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial. Nature Medicine, 27:1451-1457, Aug 2021. URL: https://doi.org/10.1038/s41591-021-01455-x, doi:10.1038/s41591-021-01455-x. This article has 162 citations and is from a highest quality peer-reviewed journal.

15. (street2021clinicalprogressionof pages 1-2): Duncan Street, Maura Malpetti, Timothy Rittman, Boyd C P Ghosh, Alexander G Murley, Ian Coyle-Gilchrist, Luca Passamonti, and James B Rowe. Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants. Brain Communications, Sep 2021. URL: https://doi.org/10.1093/braincomms/fcab206, doi:10.1093/braincomms/fcab206. This article has 35 citations and is from a peer-reviewed journal.

16. (tian2023efficacyoffaecal pages 1-2): Haiyan Tian, Jiuqi Wang, Renyi Feng, Rui Zhang, Han Liu, Chi Qin, Lin Meng, Yongkang Chen, Yu Fu, Dongxiao Liang, Xin Yuan, Yanping Zhai, Qingyong Zhu, Lingjing Jin, Junfang Teng, Xuebing Ding, and Xuejing Wang. Efficacy of faecal microbiota transplantation in patients with progressive supranuclear palsy-richardson's syndrome: a phase 2, single centre, randomised clinical trial. Apr 2023. URL: https://doi.org/10.1016/j.eclinm.2023.101888, doi:10.1016/j.eclinm.2023.101888. This article has 31 citations and is from a peer-reviewed journal.

17. (murthy2024dnamethylationpatterns pages 1-2): Megha Murthy, Katherine Fodder, Yasuo Miki, Naiomi Rambarack, Eduardo De Pablo Fernandez, Lasse Pihlstrøm, Jonathan Mill, Thomas T. Warner, Tammaryn Lashley, and Conceição Bettencourt. Dna methylation patterns in the frontal lobe white matter of multiple system atrophy, parkinson’s disease, and progressive supranuclear palsy: a cross-comparative investigation. Acta Neuropathologica, Jul 2024. URL: https://doi.org/10.1007/s00401-024-02764-4, doi:10.1007/s00401-024-02764-4. This article has 14 citations and is from a highest quality peer-reviewed journal.

18. (forrest2023cellspecificmaptgene pages 1-2): Shelley L. Forrest, Seojin Lee, Nasna Nassir, Ivan Martinez-Valbuena, Valerie Sackmann, Jun Li, Awab Ahmed, Maria Carmela Tartaglia, Lars M. Ittner, Anthony E. Lang, Mohammed Uddin, and Gabor G. Kovacs. Cell-specific mapt gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy. Acta Neuropathologica, 146:395-414, Jun 2023. URL: https://doi.org/10.1007/s00401-023-02604-x, doi:10.1007/s00401-023-02604-x. This article has 45 citations and is from a highest quality peer-reviewed journal.

19. (whitney2024singlecelltranscriptomicand pages 12-14): Kristen Whitney, Won-Min Song, Abhijeet Sharma, Diana K. Dangoor, Kurt Farrell, Margaret M. Krassner, Hadley W. Ressler, Thomas D. Christie, Shrishtee Kandoi, Ruth H. Walker, Melissa J. Nirenberg, Steven J. Frucht, Giulietta M. Riboldi, Bin Zhang, Ana C. Pereira, and John F. Crary. Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy. Acta Neuropathologica, Dec 2024. URL: https://doi.org/10.1007/s00401-024-02823-w, doi:10.1007/s00401-024-02823-w. This article has 15 citations and is from a highest quality peer-reviewed journal.

20. (farrell2024genetictranscriptomichistological pages 4-7): Kurt Farrell, Jack Humphrey, Timothy Chang, Yi Zhao, Yuk Yee Leung, Pavel P Kuksa, Vishakha Patil, Wan-Ping Lee, Amanda B. Kuzma, Otto Valladares, Laura B. Cantwell, Hui Wang, Ashvin Ravi, Claudia De Sanctis, Natalia Han, Thomas D. Christie, Kristen Whitney, Margaret M. Krassner, Hadley Walsh, SoongHo Kim, Diana Dangoor, Megan A. Iida, Alicia Casella, Ruth H. Walker, Melissa J. Nirenberg, Alan E. Renton, Bergan Babrowicz, Giovanni Coppola, Towfique Raj, Günter U. Höglinger, Lawrence I. Golbe, Huw R. Morris, John Hardy, Tamas Revesz, Tom T. Warner, Zane Jaunmuktane, Kin Y. Mok, Rosa Rademakers, Dennis W. Dickson, Owen A. Ross, Li-San Wang, Alison Goate, Gerard Schellenberg, Daniel H. Geschwind, John F. Crary, and Adam Naj. Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2023.11.09.565552, doi:10.1101/2023.11.09.565552. This article has 58 citations.

21. (jang2024biomarkerdiscoveryin pages 1-2): Yura Jang, Sungtaek Oh, Anna J. Hall, Zhen Zhang, Thomas F. Tropea, Alice Chen-Plotkin, Liana S. Rosenthal, Ted M. Dawson, Chan Hyun Na, and Alexander Y. Pantelyat. Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid. Clinical Proteomics, Sep 2024. URL: https://doi.org/10.1186/s12014-024-09507-3, doi:10.1186/s12014-024-09507-3. This article has 9 citations and is from a peer-reviewed journal.

22. (boxer2017advancesinprogressive pages 1-2): Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, and Günter U Höglinger. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Jul 2017. URL: https://doi.org/10.1016/s1474-4422(17)30157-6, doi:10.1016/s1474-4422(17)30157-6. This article has 515 citations and is from a highest quality peer-reviewed journal.

23. (cristiani2024serumtauspecies pages 1-2): Costanza Maria Cristiani, Luana Scaramuzzino, Elvira Immacolata Parrotta, Giovanni Cuda, Aldo Quattrone, and Andrea Quattrone. Serum tau species in progressive supranuclear palsy: a pilot study. Diagnostics, 14:2746, Dec 2024. URL: https://doi.org/10.3390/diagnostics14232746, doi:10.3390/diagnostics14232746. This article has 2 citations.

24. (dilcher2024linkingpi2620taupet pages 1-5): Roxane Dilcher, Charles B. Malpas, William T. O’Brien, Stuart J. McDonald, Craig Despott, Kelly Bertram, Matthew P. Pase, Meng Law, Terence J. O’Brien, and Lucy Vivash. Linking pi-2620 tau-pet, fluid biomarkers, mri, and cognition to advance diagnostics for progressive supranuclear palsy. MedRxiv, Oct 2024. URL: https://doi.org/10.1101/2024.10.14.24315486, doi:10.1101/2024.10.14.24315486. This article has 2 citations.

25. (boxer2017advancesinprogressive pages 4-5): Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, and Günter U Höglinger. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Jul 2017. URL: https://doi.org/10.1016/s1474-4422(17)30157-6, doi:10.1016/s1474-4422(17)30157-6. This article has 515 citations and is from a highest quality peer-reviewed journal.

26. (hoglinger2021safetyandefficacy pages 1-2): Günter U Höglinger, Irene Litvan, Nuno Mendonca, Deli Wang, Hui Zheng, Beatrice Rendenbach-Mueller, Hoi-Kei Lon, Ziyi Jin, Nahome Fisseha, Kumar Budur, Michael Gold, Davis Ryman, Hana Florian, Anwar Ahmed, Ikuko Aiba, Alberto Albanese, Kelly Bertram, Yvette Bordelon, James Bower, Jared Brosch, Daniel Claassen, Carlo Colosimo, Jean-Christophe Corvol, Paola Cudia, Antonio Daniele, Luc Defebvre, Erika Driver-Dunckley, Antoine Duquette, Roberto Eleopra, Alexandre Eusebio, Victor Fung, David Geldmacher, Lawrence Golbe, Francisco Grandas, Deborah Hall, Taku Hatano, Günter U Höglinger, Lawrence Honig, Jennifer Hui, Diana Kerwin, Akio Kikuchi, Thomas Kimber, Takashi Kimura, Rajeev Kumar, Irene Litvan, Peter Ljubenkov, Stefan Lorenzl, Albert Ludolph, Zoltan Mari, Nikolaus McFarland, Wassilios Meissner, Pablo Mir Rivera, Hidek Mochizuki, John Morgan, Renato Munhoz, Noriko Nishikawa, John O`Sullivan, Tomoko Oeda, Hideki Oizumi, Osamu Onodera, Fabienne Ory-Magne, Elizabeth Peckham, Ronald Postuma, Aldo Quattrone, Joseph Quinn, Stefano Ruggieri, Justyna Sarna, Paul E Schulz, John Slevin, Michele Tagliati, Daryl Wile, Zbigniew Wszolek, Tao Xie, and Theresa Zesiewicz. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. The Lancet Neurology, 20:182-192, Mar 2021. URL: https://doi.org/10.1016/s1474-4422(20)30489-0, doi:10.1016/s1474-4422(20)30489-0. This article has 171 citations and is from a highest quality peer-reviewed journal.

27. (hoglinger2021safetyandefficacy pages 6-7): Günter U Höglinger, Irene Litvan, Nuno Mendonca, Deli Wang, Hui Zheng, Beatrice Rendenbach-Mueller, Hoi-Kei Lon, Ziyi Jin, Nahome Fisseha, Kumar Budur, Michael Gold, Davis Ryman, Hana Florian, Anwar Ahmed, Ikuko Aiba, Alberto Albanese, Kelly Bertram, Yvette Bordelon, James Bower, Jared Brosch, Daniel Claassen, Carlo Colosimo, Jean-Christophe Corvol, Paola Cudia, Antonio Daniele, Luc Defebvre, Erika Driver-Dunckley, Antoine Duquette, Roberto Eleopra, Alexandre Eusebio, Victor Fung, David Geldmacher, Lawrence Golbe, Francisco Grandas, Deborah Hall, Taku Hatano, Günter U Höglinger, Lawrence Honig, Jennifer Hui, Diana Kerwin, Akio Kikuchi, Thomas Kimber, Takashi Kimura, Rajeev Kumar, Irene Litvan, Peter Ljubenkov, Stefan Lorenzl, Albert Ludolph, Zoltan Mari, Nikolaus McFarland, Wassilios Meissner, Pablo Mir Rivera, Hidek Mochizuki, John Morgan, Renato Munhoz, Noriko Nishikawa, John O`Sullivan, Tomoko Oeda, Hideki Oizumi, Osamu Onodera, Fabienne Ory-Magne, Elizabeth Peckham, Ronald Postuma, Aldo Quattrone, Joseph Quinn, Stefano Ruggieri, Justyna Sarna, Paul E Schulz, John Slevin, Michele Tagliati, Daryl Wile, Zbigniew Wszolek, Tao Xie, and Theresa Zesiewicz. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. The Lancet Neurology, 20:182-192, Mar 2021. URL: https://doi.org/10.1016/s1474-4422(20)30489-0, doi:10.1016/s1474-4422(20)30489-0. This article has 171 citations and is from a highest quality peer-reviewed journal.

28. (boxer2017advancesinprogressive pages 8-9): Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, and Günter U Höglinger. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Jul 2017. URL: https://doi.org/10.1016/s1474-4422(17)30157-6, doi:10.1016/s1474-4422(17)30157-6. This article has 515 citations and is from a highest quality peer-reviewed journal.

29. (barer2023progressivesupranuclearpalsy’s pages 4-5): Yael Barer, Raanan Cohen, Meital Grabarnik-John, Xiaolan Ye, Jorge Zamudio, Tanya Gurevich, and Gabriel Chodick. Progressive supranuclear palsy’s economical burden: the use and costs of healthcare resources in a large health provider in israel. Journal of Neurology, 270:3770-3778, Apr 2023. URL: https://doi.org/10.1007/s00415-023-11714-1, doi:10.1007/s00415-023-11714-1. This article has 2 citations and is from a domain leading peer-reviewed journal.

30. (bravo2024humanipsc4r pages 1-3): Celeste Parra Bravo, A. Giani, Jesus Madero Perez, Zeping Zhao, Yuansong Wan, Avi J. Samelson, M. Wong, Alessandro Evangelisti, Ethan Cordes, Li Fan, Pearly Ye, Daphne Zhu, Tatyana Pozner, Maria Mercedes, Tark Patel, Allan Yarahmady, G. Carling, Fredrik H. Sterky, Virginia M. Y. Lee, Edward B. Lee, M. DeTure, Dennis W. Dickson, Manu Sharma, S. Mok, Wenjie Luo, Mingrui Zhao, M. Kampmann, Shiaoching Gong, and Li Gan. Human ipsc 4r tauopathy model uncovers modifiers of tau propagation. Cell, 187:2446-2464.e22, Mar 2024. URL: https://doi.org/10.1016/j.cell.2024.03.015, doi:10.1016/j.cell.2024.03.015. This article has 76 citations and is from a highest quality peer-reviewed journal.

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