Research Reports - Factor associated with an increased risk for subsequent development of Alzheimer's disease after TBI

J Alzheimers Dis. 2012 Apr 27. [Epub ahead of print]

Original title: Elevated Plasma MCP-1 Concentration Following Traumatic Brain Injury as a
Potential "Predisposition" Factor Associated with an Increased Risk for Subsequent Development of Alzheimer's Disease.

Ho L, Zhao W, Dams-O'Connor K, Tang CY, Gordon W, Peskind ER, Yemul S,
Haroutunian V, Pasinetti GM.

We explored whether changes in the expression profile of peripheral blood plasma
proteins may provide a clinical, readily accessible "window" into the brain,
reflecting molecular alterations following traumatic brain injury (TBI) that
might contribute to TBI complications. We recruited fourteen TBI and ten control
civilian participants for the study, and also analyzed banked plasma specimens
from 20 veterans with TBI and 20 control cases. Using antibody arrays and ELISA
assays, we explored differentially-regulated protein species in the plasma of TBI
compared to healthy controls from the two independent cohorts. We found three
protein biomarker species, monocyte chemotactic protein-1 (MCP-1), insulin-like
growth factor-binding protein-3, and epidermal growth factor receptor, that are
differentially regulated in plasma specimens of the TBI cases. A three-biomarker
panel using all three proteins provides the best potential criterion for
separating TBI and control cases. Plasma MCP-1 contents are correlated with the
severity of TBI and the index of compromised axonal fiber integrity in the
frontal cortex. Based on these findings, we evaluated postmortem brain specimens
from 7 mild cognitive impairment (MCI) and 7 neurologically normal cases. We
found elevated MCP-1 expression in the frontal cortex of MCI cases that are at
high risk for developing Alzheimer's disease. Our findings suggest that
additional application of the three-biomarker panel to current diagnostic
criteria may lead to improved TBI detection and more sensitive outcome measures
for clinical trials. Induction of MCP-1 in response to TBI might be a potential
predisposing factor that may increase the risk for development of Alzheimer's
disease.

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