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P3‐259: Development and implementation of a TMT‐SRM assay for the qualification of candidate biomarkers of Alzheimer's disease
Author(s) -
O'Brien Darragh P.,
Guentert Andreas,
Campbell James,
Kuhn Karsten,
Ward Malcolm A.,
Byers Helen L.,
Lovestone Simon
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1759
Subject(s) - multiplex , biomarker , biomarker discovery , chemistry , computational biology , analyte , gelsolin , chromatography , bioinformatics , proteomics , biology , biochemistry , gene , actin
Background: Traumatic brain injury (TBI) is a multi-phasic disease and following the initial impact, secondary injury is thought to contribute to death and disability. Increased oxidative stress and inflammation in the brain leads to the demise of neuronal populations and ultimately decreased brain function. Identification of neural markers such as beta-Amyloid (Ab) and neuronal specific enolase (NSE) at early time-points after injury can help us better understand the multitude of such secondary injuries following TBI and may help predict outcome in these patients. Methods: Serial CSF and blood samples were collected from patients with severe TBI (GCS 3-8) who required placement of a therapeutic ventriculostomy. Following ventriculostomy placement, CSF and blood samples were obtained every 4 hours for the 1 24 hours post-injury, then every 8 hours for post-injury days 2-5. Following collection of these samples, the levels of Ab and NSE were measured in these samples using the ELISA method. Results: Following sample analysis, we found that in TBI patients that had a good neurological outcome (as indicated by the Glasgow Coma Score), there was a great increase in the levels of Ab (w390 pg/ml) compared to patients with a bad outcome (w10 pg/ml). With respect to NSE, patients with a good outcome, exhibited high levels of NSE (between 25 and 60 ng/ ml) in the CSF at 12 hours post-injury which subsided to w5 ng/ml (normal range) at around 20 hours and sustained until day 5. In contrast, patients with a bad outcome or death, had high levels of NSE (w225 ng/ ml) in the CSF, at the later time-points, which correlated with a decrease in neurological status. Conclusions: In the TBI patients, an increase in Ab levels correlated with improved outcome, whereas a decrease in the levels of NSE correlated with a good outcome. Detection of such biomarkers may be a useful tool for determining injury severity and outcome in TBI patients. As a future direction, more patients will be studied in order to validate these findings.