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Alterations in the cerebrospinal fluid relating to apolipoprotein E after traumatic brain injury and subarachnoid haemorrhage.

Kay, A.D.; (2004) Alterations in the cerebrospinal fluid relating to apolipoprotein E after traumatic brain injury and subarachnoid haemorrhage. Doctoral thesis , University of London. Green open access

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Abstract

Background: The human gene coding for apolipoprotein E is polymorphic, and the APOE4 allele has been associated with less favourable outcome after acute brain injury including traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Experimental studies identify key roles for apoE in the central nervous system such as the scavenging and recycling of lipids for cellular maintenance and repair and formation of cerebral amyloid aggregate. Human in-vivo evidence supporting the concept that apoE is involved in the response of the brain to acute injury is sparse. Objectives: This study tests the hypothesis that apoE is involved in the response of the human brain to injury, and this role is reflected by changes in cerebrospinal fluid (CSF) apoE concentration after brain injury which correlate with injury severity and outcome. In addition it was hypothesised that changes in apoE concentration would be paralleled by changes in the composition of CSF lipoprotein particles (Lps) of which apoE is a major component. Lastly, apoE is reported to chaperone amyloid-beta peptide (Abeta), therefore we hypothesised that alteration in CSF apoE after brain injury would parallel alterations in Abeta. Methods: Enzyme linked immunosorbant assay (ELISA) was used to determine the concentration of apoE, Abeta, S100B and Tau (as surrogate markers of brain injury) in CSF from TBI and SAH patients and a non-brain injured control group. Lipoprotein particles were isolated from CSF using size exclusion chromatography and characterised in relation to cholesterol, phospholipid, apolipoprotein E, and apohpoprotein AI composition. Injury severity was determined using the Glasgow Coma Score, and clinical outcome using the Glasgow Outcome Score. Results: Compared to controls there was a sustained decrease in the concentration of apoE in the CSF after TBI and SAH which was paralleled by a depletion of apoE containing lipoprotein particles. Furthermore, CSF Abeta also decreased, and the decrease correlated with injury severity and clinical outcome. In contrast the levels of S100B and Tau in brain injury CSF was substantially elevated. Conclusion: Despite the likely leakage of plasma apolipoprotein E into the subarachnoid space at the time of brain injury, apoE in the form of LpE is cleared from the CSF within days of injury. In addition, indirect evidence suggesting apoE-Abeta interactions in-vivo support the concept that apoE may form insoluble aggregates with Abeta soon after brain injury. The finding that these alterations in the CSF correlate with injury severity and outcome provides novel indirect in-vivo evidence that apoE is important to the response of the human brain to injury.

Type: Thesis (Doctoral)
Title: Alterations in the cerebrospinal fluid relating to apolipoprotein E after traumatic brain injury and subarachnoid haemorrhage.
Identifier: PQ ETD:602809
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: http://discovery.ucl.ac.uk/id/eprint/1446867
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