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Monitoring of β-amyloid dynamics after human traumatic brain injury

Marklund, Niklas LU ; Farrokhnia, Nina; Hånell, Anders; Vanmechelen, Eugeen; Enblad, Per; Zetterberg, Henrik LU ; Blennow, Kaj LU and Hillered, Lars (2014) In Journal of Neurotrauma 31(1). p.42-55
Abstract

Epidemiological evidence links severe or repeated traumatic brain injury (TBI) to the development of Alzheimer's disease (AD). Accumulation of amyloid precursor protein (APP) occurs with high frequency after TBI, particularly in injured axons, and APP may be cleaved to amyloid-β (Aβ) peptides playing key pathophysiological roles in AD. We used cerebral microdialysis (MD) to test the hypothesis that interstitial Aβ levels are altered following TBI and are related to the injury type, cerebral energy metabolism, age of the patient, and level of consciousness. In the present report, we evaluated 10 mechanically ventilated patients (7 male, 3 female, ages 18-76 years) with a severe TBI, who had intracranial pressure and MD monitoring. Each... (More)

Epidemiological evidence links severe or repeated traumatic brain injury (TBI) to the development of Alzheimer's disease (AD). Accumulation of amyloid precursor protein (APP) occurs with high frequency after TBI, particularly in injured axons, and APP may be cleaved to amyloid-β (Aβ) peptides playing key pathophysiological roles in AD. We used cerebral microdialysis (MD) to test the hypothesis that interstitial Aβ levels are altered following TBI and are related to the injury type, cerebral energy metabolism, age of the patient, and level of consciousness. In the present report, we evaluated 10 mechanically ventilated patients (7 male, 3 female, ages 18-76 years) with a severe TBI, who had intracranial pressure and MD monitoring. Each MD sample was analyzed for hourly routine energy metabolic biomarkers (MD-lactate, MD-pyruvate, MD-glucose, and MD-lactate/pyruvate ratio), cellular distress biomarkers (MD-glutamate, MD-glycerol), and MD-urea. The remaining MD samples were analyzed for Aβ1-40 (Aβ40; n=765 samples) and Aβ1-42 (Aβ42; n=765 samples) in pooled 2 h fractions up to 14 days post-injury, using the Luminex xMAP technique, allowing detection with high temporal resolution of the key Aβ peptides Aβ40 and Aβ42. Data are presented using medians and 25th and 75th percentiles. Both Aβ40 and Aβ42 were consistently higher in patients with predominately diffuse axonal injury compared with patients with focal TBI at days 1-6 post- injury, Aβ42 being significantly increased at 113-116 h post-injury (p<0.05). The Aβ levels did not correlate with the interstitial energy metabolic situation, age of the patient, or the level of consciousness. These results support that interstitial generation of potentially toxic Aβ species may occur following human TBI, particularly related to axonal injury.

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author
organization
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Contribution to journal
publication status
published
keywords
Adolescent, Adult, Aged, Amyloid beta-Peptides, Biomarkers, Brain Injuries, Diffuse Axonal Injury, Female, Humans, Male, Microdialysis, Middle Aged, Peptide Fragments, Young Adult, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neurotrauma
volume
31
issue
1
pages
14 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:84892698570
ISSN
1557-9042
DOI
10.1089/neu.2013.2964
language
English
LU publication?
yes
id
2571b72d-c1f1-4ab3-9a94-0959221227fe
date added to LUP
2016-12-09 16:13:57
date last changed
2017-09-24 05:04:33
@article{2571b72d-c1f1-4ab3-9a94-0959221227fe,
  abstract     = {<p>Epidemiological evidence links severe or repeated traumatic brain injury (TBI) to the development of Alzheimer's disease (AD). Accumulation of amyloid precursor protein (APP) occurs with high frequency after TBI, particularly in injured axons, and APP may be cleaved to amyloid-β (Aβ) peptides playing key pathophysiological roles in AD. We used cerebral microdialysis (MD) to test the hypothesis that interstitial Aβ levels are altered following TBI and are related to the injury type, cerebral energy metabolism, age of the patient, and level of consciousness. In the present report, we evaluated 10 mechanically ventilated patients (7 male, 3 female, ages 18-76 years) with a severe TBI, who had intracranial pressure and MD monitoring. Each MD sample was analyzed for hourly routine energy metabolic biomarkers (MD-lactate, MD-pyruvate, MD-glucose, and MD-lactate/pyruvate ratio), cellular distress biomarkers (MD-glutamate, MD-glycerol), and MD-urea. The remaining MD samples were analyzed for Aβ1-40 (Aβ40; n=765 samples) and Aβ1-42 (Aβ42; n=765 samples) in pooled 2 h fractions up to 14 days post-injury, using the Luminex xMAP technique, allowing detection with high temporal resolution of the key Aβ peptides Aβ40 and Aβ42. Data are presented using medians and 25th and 75th percentiles. Both Aβ40 and Aβ42 were consistently higher in patients with predominately diffuse axonal injury compared with patients with focal TBI at days 1-6 post- injury, Aβ42 being significantly increased at 113-116 h post-injury (p&lt;0.05). The Aβ levels did not correlate with the interstitial energy metabolic situation, age of the patient, or the level of consciousness. These results support that interstitial generation of potentially toxic Aβ species may occur following human TBI, particularly related to axonal injury.</p>},
  author       = {Marklund, Niklas and Farrokhnia, Nina and Hånell, Anders and Vanmechelen, Eugeen and Enblad, Per and Zetterberg, Henrik and Blennow, Kaj and Hillered, Lars},
  issn         = {1557-9042},
  keyword      = {Adolescent,Adult,Aged,Amyloid beta-Peptides,Biomarkers,Brain Injuries,Diffuse Axonal Injury,Female,Humans,Male,Microdialysis,Middle Aged,Peptide Fragments,Young Adult,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {42--55},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Monitoring of β-amyloid dynamics after human traumatic brain injury},
  url          = {http://dx.doi.org/10.1089/neu.2013.2964},
  volume       = {31},
  year         = {2014},
}