title: Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.
abstract: Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated beta-amyloid (Abeta), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP) in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28 patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss-sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11. There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1 to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF-Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42) does not reflect Abeta metabolism in the central nervous system (CNS).
authors.affiliation: Institute of Clinical Neuroscience Section, Sahlgrenska University Hospital/Mölndal, SE-43180, Sweden. Annika.Olsson@neuro.gu.se
authors.forename: Annika
authors.initials: A
authors.lastname: Olsson
authors.forename: Ludvig
authors.initials: L
authors.lastname: Csajbok
authors.forename: Martin
authors.initials: M
authors.lastname: Ost
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.forename: Karin
authors.initials: K
authors.lastname: Nylén
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
authors.forename: Bengt
authors.initials: B
authors.lastname: Nellgård
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000150:complications*; D015984:Causality; D002552:Cerebral Ventricles / Q000378:metabolism; D020833:Diffuse Axonal Injury / Q000134:cerebrospinal fluid* / Q000209:etiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid*; D058225:Plaque, Amyloid / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)