Association of increased cortical soluble Aβ42 levels with diffuse plaques after severe brain injury in humans
Abstract
Background Traumatic brain injury (TBI) is an environmental risk factor for developing Alzheimer disease. This may be due, in part, to changes associated with beta-amyloid (Abeta) plaque formation, which can occur within hours after injury, regardless of the patient's age. In addition to being precursors of toxic fibrils that deposit into plaques, soluble (nonfibrillar) Abeta peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease. Changes in soluble Abeta levels and their relationship to Abeta plaque formation following TBI are unknown. Objective To quantify brain tissue levels of soluble Abeta peptides and their precursor protein in relation to Abeta plaque formation after TBI in humans. Design Surgically resected temporal cortex tissue from patients with severe TBI was processed for biochemical assays of soluble Abeta peptides with COOH-termini ending in amino acid 40 (Abeta(40)) or 42 (Abeta(42)) and Abeta precursor protein to compare patients with cortical Abeta plaques and those without. Patients Nineteen subjects admitted to the University of Pittsburgh Medical Center for treatment of severe closed head injury. Results Patients with severe TBI and cortical plaques had higher levels of soluble Abeta(1-42) but not Abeta(1-40); half of them were apolipoprotein E (APOE) epsilon4 allele carriers. The lowest Abeta levels were in 1 patient without plaques who was the only subject with an APOE epsilon2 allele. beta-Amylo…
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Accumulation of APP and extracellular deposition of the 40- to 42-amino acid Aβ peptide in senile plaques has been identified in human brain tissue soon after severe TBI.
“Third, accumulation of APP and extracellular deposition of the 40- to 42-amino acid Aβ peptide in senile plaques has been identified in human brain tissue soon after severe TBI (29, 30).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [30]
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- Authors
- DeKosky, S. T., Abrahamson, E. E., Ciallella, J. R., Paljug, W. R., Wisniewski, S. R., Clark, R. S. B., & Ikonomovic, M. D.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2007-04-01
- Volume
- 64
- Issue
- 4
- Pages
- 541
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W1999082266
- Cited by
- 152
- References
- 8
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 16 · 2014: 8 · 2013: 14 · 2012: 9
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 05-133, P50AG005133)
- National Institute of Neurological Disorders and Stroke (NS-30318)
- 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, soluble amyloid-beta, amyloid-beta 42, Aβ40, Alzheimer's disease risk, APOE ε4, amyloid precursor protein, temporal cortex, closed head injury, synaptic dysfunction
- MeSH terms
- Adult, Brain Injuries, Cerebral Cortex, Female, Heterozygote, Humans, Male, Middle Aged, Peptide Fragments, Solubility, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apolipoprotein E4
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