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include sample size and selection bias in helmet efficacy, injury se-
verity, and pre-morbidity.
Keywords: biomarker, concussion, eye tracking, helmet
A5-08
PERIPHERAL CONCENTRATIONS OF TOTAL TAU ARE
INCREASED IN MILITARY PERSONNEL WHO SUSTAIN
TRAUMATIC BRAIN INJURIES DURING DEPLOYMENT
Jessica Gill
1
, Anlys Olivera
1
, Natasha Lejbman
1
, Andreas Jeromin
6
,
Louis French
2,3
, Ramon Diaz-Arrastia
2,5
1
NIH, Tissue Injury Branch, Bethesda, USA
2
Center for Neuroscience and Regenerative Medicine, Center for
Neuroscience and Regenerative Medicine, Bethesda, USA
3
National Intrepid Center of Excellence, Walter Reed National Mili-
tary Medical Center, Bethesda, USA
4
Madigan Army Medical Center, Madigan Army Medical Center,
Tacoma Washington, USA
5
Uniformed Services University of the Health Sciences, Department of
Neurology, Bethesda, USA
6
Quanterix Corporation, Quanterix Corporation, Lexington, USA
Background:
Military personnel are commonly exposed to multiple
traumatic brain injuries (TBIs) during deployment, placing them at high
risk for chronic symptoms. Elevated concentrations of tau are observed in
blood acutely following a TBI, and accumulations within neurons and
glial cells are one of the pathologic hallmarks of chronic traumatic en-
cephalopathy. The role of tau elevations in blood in the onset and
maintenance of long-term symptoms after TBI has not been investigated.
Design:
Plasma total tau concentrations were measured using a novel
ultra-sensitive single-molecule enzyme-linked immunosorbent assay.
Classification of self-reported TBI
+
subjects (n
=
70) versus TBI- sub-
jects (n
=
28) was made using the Warrior Administered Retrospective
Casualty Assessment Tool, which compiles data on war-related injury
types, mechanisms, and post-injury symptoms. Group differences in tau
concentrations were determined through ANOVA models, and area-
under the curve determined the sensitivity and specificity of tau con-
centrations in predicting TBI and chronic symptoms.
Results:
Concentrations of plasma tau were significantly elevated
in subjects with TBI
+
compared to TBI- (F
1,97
=
4.97, p
=
0.03).
Within the TBI
+
cases, plasma total tau concentrations were signifi-
cantly associated with having a medical record of TBI (F
1,69
=
6.15,
p
=
0.016), as well as reporting the occurrence of three of more TBIs
during deployment (F
1,69
=
8.57, p
<
0.01).
Conclusion:
Total tau concentrations are elevated in military per-
sonnel who report multiple TBIs, and relate to symptoms of PCD,
independent of PTSD and depression. These findings suggest plasma
tau shows promise as a biomarker for chronic TBI-related symptoms.
Keywords: highly sensitive immunoassays, total tau, prognostic
biomarkers, chronic symptoms
A5-09
EXPLORING THE MOLECULAR OVERLAP IN THE BRAIN
AND PLASMA OF TBI AND AD MOUSE MODELS USING
PROTEOMIC AND LIPIDOMIC TECHNOLOGY
Moustafa Algamal
, Joseph Ojo, Jon Reed, Laila Abdullah, Gogce
Crynen, Jim Evans, Michael Mullan, Fiona Crawford
Roskamp Institute, Neurodegeneration and drug discovery, Sarasota, USA
Traumatic brain injury (TBI) is a major cause of disability in the military
and civilian population, and for many years has been known to be a major
risk factor for Alzheimer’s disease (AD). Although the existence of this
relationship is well recognized, and the overlap and distinction between
pathological features of AD and TBI, have long been the subject of
reporting and discussion, the precise nature of how TBI leads to or
precipitates AD pathogenesis is currently not understood. To address this
problem we are generating time-dependent molecular profiles of re-
sponse to TBI and AD pathogenesis in mouse models, using proteomic
and lipidomic analyses. We are using the well-validated hTau mouse
models that develops age-related tau pathological features, and our
well-established model of mTBI in C57BL/6 mice. Brain and plasma
from these animals have been collected at different ages (for hTau
mice), or at different timepoints after repetitive mTBI (C57BL/6). Liquid
chromatography/mass spectrometry (LC-MS) and in source collision
induced dissociation (SCID) approaches are being applied to develop
molecular profiles of proteins and lipid species that are significantly
differentially expressed as a consequence of AD or mTBI. We show an
age-related upregulation in phosphotidylcholine (PC/ePC) and lyso-
phosphotidylcholine (LPC) species in the plasma of both TBI and hTau
mouse models. We anticipate that the exploration of molecular profiles
from these animal models will enable us to identify cellular pathways that
have pathogenic significance in human conditions. Moreover, we further
aim to explore these identified pathways as potential targets for thera-
peutic intervention. Generation of Omic analyses are ongoing for com-
parisons of TBI profiles at 24 hrs, 3, 6, 9 and 12 months post-injury with
profiles at 3, 9 and 15 months of age in the hTau models.
Keywords: concussion, Alzheimer’s Disease, animal models, Omic
analyses
A5-10
GFAP AND UCH-L1 DURING THE FIRST WEEK AFTER A
TBI - CORRELATIONS WITH CLINICAL AND IMAGING
FINDINGS AND OUTCOME
Olli Tenovuo
1
, Jussi Posti
1
, Riikka Takala
1
, Hilkka Runtti
2
, Jonathan
Coles
3
, David Menon
3
1
Turku University Hospital, Rehabilitation and Brain Trauma, Turku,
Finland
2
VTT Technical Research Centre of Finland, Systems Medicine,
Tampere, Finland
3
University of Cambridge, Division of Anesthesia, Cambridge, United
Kingdom
Introduction:
Protein biomarkers glial fibrillary acidic protein
(GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) may help
to detect traumatic brain injury (TBI), assess its severity and improve
outcome prediction. We investigated the relation of the GFAP and
UCH-L1 levels to the severity of TBI and to outcome during the first
week after the injury.
Methods:
Serum UCH-L1 and GFAP were measured from 389
patients with acute TBI and 81 controls enrolled in a multicentre
prospective study. The measures included initial Glasgow Coma Scale
(GCS), head CT scan and blood samples (admission and on days 1, 2,
3 and 7). The outcome was assessed using Glasgow Outcome Scale
(GOS) or its extended version (GOSe).
Results:
GFAP and UCH-L1 levels on admission and during the
first two days after the injury correlated with the initial GCS. On
admission, AUC (receiver operating characteristics) for distinguishing
any pathological finding in CT was 0.739 and 0.621, for GFAP and
UCH-L1, respectively. There was a negative correlation with the
outcome and UCH-L1 and GFAP levels on the first three and two
days, respectively. For UCH-L1 to predict unfavorable outcome
(GOS
£
3), incomplete recovery (GOSe
£
8) or death the AUC was
0.727, 0.538 and 0.655, respectively. For GFAP the corresponding
AUCs were 0.723, 0.628 and 0.716.
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