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

Article type: Research Article

Authors: Ho, Lap^{a; 1} | Zhao, Wei^{a; 1} | Dams-O'Connor, Kristen^b | Tang, Cheuk Y.^c | Gordon, Wayne^b | Peskind, Elaine R.^e | Yemul, Shrishailam^a | Haroutunian, Vahram^c | Pasinetti, Giulio Maria^{a; d; *}

Affiliations: [a] Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA | [b] Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY, USA | [c] Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA | [d] GRECC, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA | [e] VA Northwest Network Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA

Correspondence: [*] Correspondence to: Giulio Maria Pasinetti, MD, PhD, Department of Neurology, Mount Sinai School of Medicine, 1468 Madison Avenue, Annenberg Building, Room 20-02, New York, NY 10029, USA. Tel.: +1 212 241 7938 or +1 212 241 5563; Fax: +1 212 876 9042; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Alzheimer's disease, biomarker, long-term clinical TBI phenotypes, mild cognitive impairment, monocyte chemotactic protein-1, plasma, traumatic brain injury

DOI: 10.3233/JAD-2012-120598

Journal: Journal of Alzheimer's Disease, vol. 31, no. 2, pp. 301-313, 2012