Neuropathology of variants of progressive supranuclear palsy
Abstract
PURPOSE OF REVIEW: Neurodegenerative tauopathies, of which progressive supranuclear palsy (PSP) is one of the most common, are clinically heterogeneous, reflecting differences in distribution and biochemical composition of tau pathology. This review highlights the range of clinical and pathologic presentations of PSP and its variants. RECENT FINDINGS: Progressive supranuclear palsy is a 4R tauopathy with neuronal and glial tau-immunoreactive lesions in neuroanatomically specific nuclei in the basal ganglia, diencephalon, brainstem and cerebellum, with restricted involvement of the neocortex. Hierarchical cluster analyses of clinical and pathologic features of PSP indicate that there are distinct clinicopathologic variants of PSP. In variants of PSP presenting with focal cortical syndromes, such as frontotemporal dementia, corticobasal syndrome and apraxia of speech, there is greater cortical pathology than in typical PSP. In variants of PSP presenting with levodopa-responsive Parkinsonism, as well as pure akinesia and gait failure, there is less cortical pathology and more severe degeneration in the cardinal nuclei - globus pallidus, subthalamic nucleus and substantia nigra - than in typical PSP. SUMMARY: Clinical variants in PSP reflect varying anatomical distribution of tau pathology, but they share histopathologic, biochemical and genetic features with typical PSP. The basis for anatomical selective vulnerability in PSP and its variants remains to be determined.
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The spatial distribution of the in vivo association between microglial activation and tau pathology in PSP mirrors previous findings that tau pathology affects both subcortical and cortical regions in PSP Richardson's syndrome.
“The spatial distribution of this in vivo association between microglial activation and tau pathology in PSP mirrors previous findings showing that tau pathology affects not only subcortical but also cortical regions in PSP Richardson’s syndrome42,43.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [42]
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- Authors
- Dickson, D. W., Ahmed, Z., Algom, A. A., Tsuboi, Y., & Josephs, K. A.
- Affiliations
- Mayo Clinic (US)
- UCL Queen Square Institute of Neurology (GB)
- Assaf Harofeh Medical Center (IL)
- Fukuoka University (JP)
- Corresponding author
- Dickson, Dennis W
- Venue
- Current Opinion in Neurology
- Published
- 2010-08
- Volume
- 23
- Issue
- 4
- Pages
- 394-400
- ISSN
- 1350-7540 (ISSN-L)
- OpenAlex
- W2085875718
- Cited by
- 386
- References
- 65
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 19 · 2023: 19 · 2022: 25 · 2021: 45 · 2020: 42 · 2019: 30 · 2018: 21 · 2017: 30 · 2016: 24 · 2015: 21 · 2014: 16 · 2013: 21 · 2012: 11
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Aging (P50‐AG16574, P01AG017216, P50AG016574)
- National Institute of Neurological Disorders and Stroke (P50-NS40256, P50NS040256)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD049078, K12 HD 49078)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- progressive supranuclear palsy, tauopathy, clinicopathological correlation, basal ganglia degeneration, levodopa-responsive parkinsonism, frontotemporal dementia, corticobasal syndrome, apraxia of speech, globus pallidus, subthalamic nucleus, substantia nigra, selective neuronal vulnerability
- MeSH terms
- Brain, Humans, Neurons, Phenotype, Supranuclear Palsy, Progressive, tau Proteins, Tauopathies
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