Distribution and characteristics of transactive response DNA binding protein 43 kDa pathology in progressive supranuclear palsy
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Background: This study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it. Methods: Hippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed. Results: We observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies. Conclusions: Distribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP‐vulnerable regions are also susceptible to this non‐tau pathology. © 2016 International Parkinson and Movement Disorder Society.
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Most of the assessed FTD cases displayed tauopathies rather than TDP-43 inclusions, negating TDP-43's potential involvement.
“However, only a small subset of PSP cases, which predominantly comprised the FTD group, have reported TDP‐43 intracellular inclusions subsequently spreading to prefrontal cortices, and most of our assessed cases rather displayed tauopathies, negating their potential involvement. 63”
From High vulnerability of medial prefrontal pyramidal neurons in post-stroke, vascular, Alzheimer's disease, and aging-related dementias (2026) · cites this paper as [63]
The Results report TDP-43 pathology in a small minority of PSP cases and describe middle frontal gyrus involvement at a later stage (pages unavailable in our copy). They do not establish that the affected PSP cases predominantly belonged to an FTD group. The statement about “our assessed cases” is the citing authors’ own finding, not a result attributed to this source. (LLM, conf=0.85)
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- Authors
- Koga, S., Sanchez‐Contreras, M., Josephs, K. A., Uitti, R. J., Graff‐Radford, N., van Gerpen, J. A., Cheshire, W. P., Wszolek, Z. K., Rademakers, R., & Dickson, D. W.
- Affiliations
- Mayo Clinic (US)
- Department of Neuroscience Mayo Clinic Jacksonville Florida USA
- Department of Neurology Mayo Clinic Jacksonville Florida USA
- Corresponding author
- Dickson, Dennis W.
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2016-12-23
- Volume
- 32
- Issue
- 2
- Pages
- 246-255
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC5933946
- OpenAlex
- W2563474251
- Cited by
- 63
- References
- 45
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 6
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01‐DC010367, R01‐DC012519, R01‐AG037491, P50‐NS072187, R01‐NS057567, R01‐NS076471, R01‐NS080882, P50‐AG016574, P01‐AG003949)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- progressive supranuclear palsy, TDP-43 pathology, hippocampal sclerosis, amygdala, tau burden, argyrophilic grain disease, Alzheimer's disease pathology, disease stage, genetic risk factors, age of onset, cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Amygdala, DNA-Binding Proteins, Female, Hippocampus, Humans, Male, Supranuclear Palsy, Progressive, Comorbidity, TDP-43 Proteinopathies
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