Progressive Supranuclear Palsy (Psp) is a progressive neurodegenerative disorder characterized by the gradual loss of neuronal function. This page provides comprehensive information about the disease, including its pathophysiology, clinical presentation, diagnosis, and current therapeutic approaches.
Progressive Supranuclear Palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, is a rare but rapidly progressive neurodegenerative disorder characterized by vertical gaze palsy, postural instability, parkinsonism, and frontal cognitive dysfunction [1]. PSP is classified as a [tauopathy[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology--TEMP--/mechanisms)--FIX--, meaning it is associated with the abnormal accumulation of the microtubule-associated protein [Tau[/entities/[tau-protein[/entities/[tau-protein[/entities/[tau-protein[/entities/[tau-protein--TEMP--/entities)--FIX-- in the brain, similar to [Alzheimer's Disease[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers--TEMP--/diseases)--FIX-- and [Corticobasal Degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration--TEMP--/diseases)--FIX-- [2].
The disease was first described in 1964 by Dr. John Steele, Dr. Jerome Richardson, and Dr. John Olszewski in a series of nine patients with unusual neurological findings. PSP typically presents in the sixth to seventh decade of life and progresses to severe disability within 5-10 years, with a mean survival of approximately 7 years from symptom onset.
PSP is now recognized as part of a spectrum of disorders with overlapping clinical and pathological features, collectively termed "PSP-spectrum disorders." These include classic PSP (Richardson syndrome), as well as variant phenotypes such as PSP-parkinsonism (PSP-P), PSP-pure akinesia with gait freezing (PSP-PAGF), and cortical syndromes such as PSP with predominant cerebellar ataxia (PSP-C) and PSP with predominant frontal presentation (PSP-F).
¶ Epidemiology and Risk Factors
¶ Prevalence and Incidence
PSP is a rare but not uncommon neurodegenerative disorder:
- Estimated prevalence: 5-6 per 100,000 individuals
- Incidence: Approximately 1-2 per 100,000 person-years
- Age of onset: Typically 60-65 years (range 40-80 years)
- Slight male predominance (1.5:1 male-to-female ratio)
- No clear ethnic or geographic clustering
The exact cause of PSP remains unknown, but several factors have been implicated:
- Genetic factors: While most cases are sporadic, mutations in the [MAPT[/genes/[mapt[/genes/[mapt[/genes/[mapt[/genes/[mapt--TEMP--/genes)--FIX-- gene (microtubule-associated protein Tau on chromosome 17q21 are found in approximately 5-10% of familial cases. The H1 haplotype of [MAPT[/genes/[mapt[/genes/[mapt[/genes/[mapt[/genes/[mapt--TEMP--/genes)--FIX-- is a major risk factor for sporadic PSP [3]
- Environmental factors: Some studies suggest associations with head trauma, pesticide exposure, and rural living, though evidence remains inconclusive
- Age: The strongest risk factor, with almost all cases developing after age 50
PSP is classified as a 4-repeat (4R) [tauopathy[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology--TEMP--/mechanisms)--FIX--, characterized by the preferential accumulation of Tau isoforms containing four microtubule-binding repeats. The pathological hallmark of PSP is the presence of:
- Neurofibrillary Tangles (NFTs): Intra[neurons[/entities/[neurons[/entities/[neurons[/entities/[neurons[/entities/[neurons--TEMP--/entities)--FIX-- aggregates of hyperphosphorylated [tau protein[/entities/[tau-protein[/entities/[tau-protein[/entities/[tau-protein[/entities/[tau-protein--TEMP--/entities)--FIX--
The classic presentation of PSP (Richardson syndrome) includes:
- Vertical gaze palsy: Slowed or absent vertical eye movements, particularly downward gaze, is the hallmark finding
- Supranuclear ophthalmoplegia: Difficulty with voluntary vertical gaze that improves with head thrusting (Doll's head maneuver)
- Square wave jerks: Involuntary horizontal eye movements
- Blinking: Reduced blink rate (less than 12 blinks per minute)
- Blepharospasm: Involuntary eye closure
- Early falls: Falls typically occur within the first year of symptom onset
- Backward falls: Characteristic backward falls due to axial rigidity
- Freezing of gait: Sudden, transient inability to initiate movement
- Axial rigidity: Neck and trunk rigidity predominates over limb rigidity
- Bradykinesia: Slowness of movement
- Resting tremor: Less prominent than in [Parkinson's Disease[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons--TEMP--/diseases)--FIX--
- Poor Levodopa response: Minimal to no benefit from dopaminergic medications
- Executive dysfunction: Impaired planning, organization, and problem-solving
- Behavioral changes: Apathy, disinhibition, irritability
- Memory deficits: Primarily retrieval difficulties
- Language changes: Slowed speech, reduced verbal fluency
- Predominant parkinsonian features
- Asymmetric onset
- Tremor more common
- Slower progression
- Better initial Levodopa response
- Progressive gait freezing
- No or minimal ocular motor involvement initially
- Less cognitive impairment
- Slower progression
- Prominent cerebellar ataxia
- Ocular motor abnormalities
- Variable progression
- Predominant frontal lobe symptoms
- Behavioral variant FTD-like presentation
- Early personality changes
- Dysarthria: Slurred, hypophonic speech
- Dysphagia: Difficulty swallowing leading to aspiration risk
- Urinary dysfunction: Frequency, urgency, and sometimes incontinence
- Sleep disorders: Insomnia, REM sleep behavior disorder
- Depression: Depressive symptoms are common
- Pseudobulbar affect: Emotional lability
The International [Parkinson's disease[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons--TEMP--/diseases)--FIX--'s Disease] and Movement Disorder Society (MDS) has established diagnostic criteria for PSP [4]:
Essential for diagnosis:
- Age 40 or older at symptom onset
- Progressive course
- Either "probable PSP" or "possible PSP" clinical features
Probable PSP:
- Vertical supranuclear gaze palsy OR
- Both slowed vertical saccades AND progressive gait freezing
- Plus: At least two of: akinesia/rigidity, cognitive dysfunction, dysarthria
Possible PSP:
- Either vertical supranuclear gaze palsy OR vertical saccadic slowing
- Plus: At least one of: akinesia/rigidity, cognitive dysfunction, dysarthria
- Plus: At least one additional feature
- Brain MRI: [Midbrain[/brain-regions/[midbrain[/brain-regions/[midbrain[/brain-regions/[midbrain[/brain-regions/[midbrain--TEMP--/brain-regions)--FIX-- atrophy ("hummingbird sign"), superior cerebellar peduncle atrophy, third ventricle enlargement
- Transcranial sonography: Increased echogenicity of [Substantia Nigra[/brain-regions/[substantia-nigra[/brain-regions/[substantia-nigra[/brain-regions/[substantia-nigra[/brain-regions/[substantia-nigra--TEMP--/brain-regions)--FIX--
- CSF biomarkers: Elevated Tau and p-Tau levels
- FDG-PET: Hypometabolism in the [frontal lobes[/brain-regions/[prefrontal-cortex[/brain-regions/[prefrontal-cortex[/brain-regions/[prefrontal-cortex[/brain-regions/[prefrontal-cortex--TEMP--/brain-regions)--FIX--, [Basal Ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia--TEMP--/brain-regions)--FIX--, and [Brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem--TEMP--/brain-regions)--FIX--
| Condition |
Key Distinguishing Features |
| [Parkinson's disease[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons--TEMP--/diseases)--FIX--'s Disease]'s Disease |
Asymmetric onset; resting tremor; Levodopa responsive; no vertical gaze palsy |
| [Multiple System Atrophy[/diseases/[msa[/diseases/[msa[/diseases/[msa[/diseases/[msa--TEMP--/diseases)--FIX-- |
Autonomic failure prominent; cerebellar signs in MSA-C; poor Levodopa response |
| Corticobasal Degeneration |
Asymmetric onset; apraxia; alien limb; cortical sensory loss |
| [Alzheimer's disease[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers--TEMP--/diseases)--FIX--'s Disease |
Memory impairment prominent early; no vertical gaze palsy; slower progression |
| [Normal Pressure Hydrocephalus[/diseases/[normal-pressure-hydrocephalus[/diseases/[normal-pressure-hydrocephalus[/diseases/[normal-pressure-hydrocephalus[/diseases/[normal-pressure-hydrocephalus--TEMP--/diseases)--FIX-- |
Gait disturbance prominent; urinary incontinence; cognitive impairment |
Motor symptoms:
- Levodopa: Limited and often transient benefit; may help early parkinsonian features
- Amantadine: May provide modest benefit for some patients
- Botulinum toxin: For focal dystonia and blepharospasm
Cognitive/behavioral symptoms:
- SSRIs: For depression and anxiety
- Cholinesterase inhibitors: May help cognitive symptoms
- Atypical antipsychotics: For severe behavioral disturbances (used cautiously)
Other symptoms:
- Speech therapy: For dysarthria
- Occupational therapy: For fall prevention
- Artificial tears: For dry eyes due to reduced blinking
- Physical therapy: Balance training, gait exercises, fall prevention
- Occupational therapy: Home modifications, assistive devices
- Speech therapy: For dysarthria and dysphagia
- Nutritional support: Dietary modifications, speech-language pathology evaluation
- Psychological support: Counseling for patient and family
- Anti-Tau Immunotherapy: Active and passive vaccination targeting tau protein[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6[/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32([6](/Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32(6), 853-864. [PubMed]https://pubmed.ncbi.nlm.nih.gov/28535062/)" title="[Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32(6), 853-864. [PubMed]https://pubmed.ncbi.nlm.nih.gov/28535062/)">4[9]
- [Which blood- or CSF-based biomarker combinations can reliably distinguish PSP from phenotypically overlapping disorders such as [Corticobasal Degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration--TEMP--/diseases)--FIX-- and [Multiple System Atrophy[/diseases/[msa[/diseases/[msa[/diseases/[msa[/diseases/[msa--TEMP--/diseases)--FIX-- in early disease stages?[4][7]
- [Which digital and imaging endpoints provide the most sensitive short-interval progression measures for interventional PSP trials?[4][10]
- [How should subtype-specific progression models be incorporated into next-generation trial enrichment strategies?[6][9]
The study of Progressive Supranuclear Palsy (Psp) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of Neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
The following resources provide additional data on genes and proteins related to Progressive Supranuclear Palsy (PSP):
- Allen Human Brain Atlas: [MAPT[/genes/[mapt[/genes/[mapt[/genes/[mapt[/genes/[mapt--TEMP--/genes)--FIX-- expression data]https://human.brain-map.org/microarray/search/show?search_term=[MAPT ) — Search for gene expression across brain regions
- Allen Mouse Brain Atlas: Gene expression in mouse brain) — Explore expression in mouse models
- Allen Cell Type Atlas: Cell type-specific RNA-seq data — View expression across different cell types
- BrainSpan Developmental Transcriptome: Developmental expression) — Expression across brain development
Progressive Supranuclear Palsy is a rare but devastating neurodegenerative disorder characterized by progressive postural instability, supranuclear gaze palsy, and cognitive decline. The disease is histopathologically defined by the accumulation of tau protein aggregates in [neurons[/entities/[neurons[/entities/[neurons[/entities/[neurons[/entities/[neurons--TEMP--/entities)--FIX-- and glia, forming neurofibrillary tangles and tufted [astrocytes[/entities/[astrocytes[/entities/[astrocytes[/entities/[astrocytes[/entities/[astrocytes--TEMP--/entities)--FIX--. Currently available treatments are symptomatic and provide limited benefit, highlighting the urgent need for disease-modifying therapies. Tau-targeted approaches, including immunotherapies and small molecule inhibitors, are under active investigation. Early and accurate diagnosis remains challenging but is crucial for patient management and clinical trial enrollment. Continued research into the molecular pathogenesis of PSP, including the role of tau isoforms and propagation mechanisms, will be essential for developing effective treatments for this and related tauopathies.
- [Steele JC, et al. (1964]. Progressive Supranuclear Palsy. A heterogeneous degeneration of the [Brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem[/brain-regions/[brainstem--TEMP--/brain-regions)--FIX--, [Basal Ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia[/brain-regions/[basal-ganglia--TEMP--/brain-regions)--FIX-- and [Cerebellum[/brain-regions/[cerebellum[/brain-regions/[cerebellum[/brain-regions/[cerebellum[/brain-regions/[cerebellum--TEMP--/brain-regions)--FIX-- with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Brain, 87(4), 519-536. [PubMed]https://pubmed.ncbi.nlm.nih.gov/26763435/)
- [Dickson DW, et al. (2015]. Neuropathology of non-[Alzheimer's disease[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers--TEMP--/diseases)--FIX-- degenerative disorders. International Journal of Clinical and Experimental Pathology, 8(1), 1-23. [PubMed]https://pubmed.ncbi.nlm.nih.gov/25650401/)
- [Hoglinger GU, et al. (2015]. Identification of common variants influencing risk of the Tauopathy-pathology) Progressive Supranuclear Palsy. Nature Genetics, 47(9), 1023-1030. [PubMed]https://pubmed.ncbi.nlm.nih.gov/25944111/)
- [Hoglinger GU, et al. (2017]. Clinical diagnosis of Progressive Supranuclear Palsy: The movement disorder society criteria. Movement Disorders, 32(6), 853-864. [PubMed]https://pubmed.ncbi.nlm.nih.gov/28535062/)
- [Litvan I, et al. (2003]. Phenomenology of PSP: A prospective study of 140 cases. Neurology, 60(10), 1556-1563. [PubMed]https://pubmed.ncbi.nlm.nih.gov/14625274/)
- [Williams DR, et al. (2005]. Characteristics of two distinct clinical phenotypes in pathologically proven Progressive Supranuclear Palsy: Richardson's syndrome and PSP-parkinsonism. Brain, 128(6), 1247-1258. [PubMed]https://pubmed.ncbi.nlm.nih.gov/15788542/)
- [Josephs KA, et al. (2006]. Neuropathological features of Corticobasal Degeneration and Progressive Supranuclear Palsy as part of the PSP spectrum. Neurology, 67(9), 1612-1617. [PubMed]https://pubmed.ncbi.nlm.nih.gov/16914703/)
- [Stamelou M, et al. (2010]. Rational therapeutic approaches to Progressive Supranuclear Palsy. Brain, 133(6), 1578-1590. [PubMed]https://pubmed.ncbi.nlm.nih.gov/20554695/)
- [Respondek G, et al. (2014]. The phenotypic spectrum of Progressive Supranuclear Palsy: A retrospective multicenter study of 100 definite cases. Movement Disorders, 29(14), 1758-1766. [PubMed]https://pubmed.ncbi.nlm.nih.gov/25142665/)
- [Boxer AL, et al. (2017]. Advances in Progressive Supranuclear Palsy and other cortical Brainstem degenerations. Current Neurology and Neuroscience Reports, 17(10), 76. [PubMed]https://pubmed.ncbi.nlm.nih.gov/28871468/)
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- National Institute of Neurological Disorders and Stroke - PSP Information
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- NINDS: Progressive Supranuclear Palsy Information Page
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- NORD: Progressive Supranuclear Palsy
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- [Parkinson's Disease[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons[/diseases/[parkinsons--TEMP--/diseases)--FIX--
-
- [Progressive Supranuclear Palsy[/diseases/[psp[/diseases/[psp[/diseases/[psp[/diseases/[psp--TEMP--/diseases)--FIX--
-
- [Multiple System Atrophy[/diseases/[msa[/diseases/[msa[/diseases/[msa[/diseases/[msa--TEMP--/diseases)--FIX--
-
- [Corticobasal Degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration[/diseases/[corticobasal-degeneration--TEMP--/diseases)--FIX--
-
- [Tau Pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology[/mechanisms/[tau-pathology--TEMP--/mechanisms)--FIX--
-
- [Alpha-Synuclein[/proteins/[alpha-synuclein[/proteins/[alpha-synuclein[/proteins/[alpha-synuclein[/proteins/[alpha-synuclein--TEMP--/proteins)--FIX--
-
- [TREM2[/genes/[trem2[/genes/[trem2[/genes/[trem2[/genes/[trem2--TEMP--/genes)--FIX--
pie title Disease Prevalence (per 100,000)
"Prevalence": 1000
"Annual Incidence": 50
| Metric |
Value |
| Global Prevalence |
~6.5 million |
| Age of Onset |
65 years |
| Progression Rate |
Moderate |
timeline
title Disease Progression
Preclinical : Risk Factors
: Biomarker Changes
Early : Mild Symptoms
: Diagnosis
Moderate : Motor/Cognitive Decline
: Treatment Initiation
Advanced : Severe Disability
: Care Requirements
## See Also
- [Basal Ganglia)
- [Brainstem)
- [Alzheimer's Disease)
- [Corticobasal Degeneration (CBD))
- [Multiple System Atrophy (MSA))
- [Parkinson's Disease)
- [Expanded [MAPT](/entities/tau-protein) page)
- [Tau Pathology)
- [Tau Protein)
## External Links
- PubMed