CoChat
Sign Up
Cited by 87Traumatic Brain Injury ResearchAmyotrophic Lateral Sclerosis ResearchTraumatic Brain Injury and Neurovascular Disturbances

Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans

Open access
Johnson, Victoria E., Stewart, William, Trojanowski, John Q., Smith, Douglas H.·2011·Acta Neuropathologica
DOI 10.1007/s00401-011-0909-9PMC PMC3979333
Open this paper in CoChat — free account

Abstract

The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer's disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43) and phosphorylation-independent TDP-43 (pi-TDP-43), we examined acute (n = 23: Survival < 2 weeks) and long-term (n = 39; 1-47 years survival) survivors of a single TBI versus age-matched controls (n = 47). Multiple regions were examined including the hippocampus, medial temporal lobe, cingulate gyrus, superior frontal gyrus and brainstem. No association was found between a history of single TBI and abnormally phosphorylated TDP-43 (p-TDP-43) inclusions. Specifically, just 3 of 62 TBI cases displayed p-TDP-43 pathology versus 2 of 47 control cases. However, while aggregates of p-TDP-43 were not increased acutely or long-term following TBI, immunoreactivity to phosphorylation-independent TDP-43 was commonly increased in the cytoplasm following TBI with both acute and long-term survival. Moreover, while single TBI can induce multiple long-term neurodegenerative changes, the absence of TDP-43 proteinopathy may indicate a fundamental difference in the processes induced following single TBI from those of repetitive TBI.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00401-011-0909-9

Cites

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Other studies indicate that neuroinflammation, b-amyloid deposition, and accumulation of TDP-43 and p-tau can arise following a single moderate-severe TBI, and there is emerging evidence that multiple types of neuropathology can be present following repetitive mild TBI.

    “There are other studies, however, indicating that different types of neuropathology, such as neuroinflammation (36), b-amyloid deposition (37), and accumulation of TDP-43 (38) and p-tau (37, 39, 40) can and do arise following a single moderate-severe TBI (41)(42)(43), and there is emerging evidence that multiple types of neuropathology can be present following repetitive mild TBI (43,44).”

    From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [38]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 78 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Johnson, V. E., Stewart, W., Trojanowski, J. Q., & Smith, D. H.
Affiliations
  • University of Glasgow (GB)
  • University of Pennsylvania (US)
Corresponding author
Smith, Douglas H.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2011-11-19
Volume
122
Issue
6
Pages
715-726
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-011-0909-9
PMC
PMC3979333
OpenAlex
W2012342339
Cited by
87
References
78
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 2 · 2019: 15 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 2 · 2013: 9 · 2012: 4
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
Funders
  • National Institutes of Health (5r01ag017546-02)
  • National Institute on Aging (AG17546, P30AG010124, AG-10124, R03AG038911)
  • National Institute of Neurological Disorders and Stroke (NS-038104, R01NS038104, P01NS056202, NS 056202)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
TDP-43, traumatic brain injury, TDP-43 proteinopathy, chronic traumatic encephalopathy, FTLD-TDP, amyotrophic lateral sclerosis, neurodegeneration, long-term survival, hippocampus, brainstem
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Brain Injuries, Brain Stem, Child, DNA-Binding Proteins, Female, Gyrus Cinguli, Hippocampus, Humans, Male, Middle Aged, Phosphorylation, Temporal Lobe, Time Factors, Survival Rate, Case-Control Studies, Brain Injury, Chronic, Young Adult, TDP-43 Proteinopathies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review