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Cited by 70Alzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research

Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer’s disease transgenic mice

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Tajiri, Naoki, Kellogg, S. Leilani, Shimizu, Toru, Arendash, Gary W., Borlongan, Cesar V.·2013·PLoS ONE
DOI 10.1371/journal.pone.0078851PMC PMC3817089
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Abstract

Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain.

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  • Many animal studies show increased production and accumulation of amyloid precursor protein (APP), Aβ, and pathological tau following TBI.

    “Second, many animal studies show increased production and accumulation of amyloid precursor protein (APP), Aβ, and pathological tau following TBI (16, 21–28).”

    From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [24]

    The Results report increased extracellular Aβ deposits after TBI in mice, and the Discussion reports another mouse study finding Aβ accumulation and increased phospho-tau immunoreactivity. The paper does not report increased production or accumulation of APP; its Discussion only proposes increased cleavage of APP to Aβ. It also does not establish the claim across “many” animal studies. (LLM, conf=0.85)

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Authors
Tajiri, N., Kellogg, S. L., Shimizu, T., Arendash, G. W., & Borlongan, C. V.
Affiliations
  • University of South Florida (US)
  • NeuroEM Therapeutics (United States) (US)
Corresponding author
Borlongan, Cesar V.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-11-04
Volume
8
Issue
11
Pages
e78851
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0078851
PMC
PMC3817089
OpenAlex
W2069828825
Cited by
70
References
37
Citations by year
2025: 1 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 10 · 2016: 8 · 2015: 13 · 2014: 3 · 2013: 1
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Celgene
  • University of South Florida
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS071956, U01NS055914)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, Alzheimer's disease, cognitive impairment, amyloid-beta deposition, APP/PS1 mice, controlled cortical impact, spatial memory, neuronal loss, MAP2, hippocampus, parietal cortex
MeSH terms
Alzheimer Disease, Animals, Brain Injuries, Cognition Disorders, Disease Models, Animal, Extracellular Space, Hippocampus, Humans, Memory, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Parietal Lobe, Time Factors, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microscopy, Confocal, Maze Learning, Mice, Presenilin-1

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