Steven T. DeKosky Professor and Chairman, Department of Neurology, Director of the Alzheimer's Disease Research Center University of Pittsburgh Phone: (412) 692-4622 Fax: (412) 692-4526 Email: DeKoskyST@upmc.edu

M.D., University of Florida Research Interests Dr. DeKosky's basic research centers on two main, inter-related areas of investigation, Alzheimer's disease (AD) and traumatic brain injury (TBI). Using a wide range of immunohistological, biochemical and molecular biological techniques, his laboratory examines the reparative mechanisms which attempt to maintain normal function in the face of chronic and acute neural injury. In AD, the major focus is on synapse loss and the correlation with cognition, cholinergic chemistry, and the pathogenesis of neuritic plaques. In models of experimental brain trauma, as well as in brain tissue and spinal fluid samples from injured human subjects, the laboratory is examining the temporal sequence of expression of beta amyloid, which is a pathogenic factor in AD but is also upregulated in TBI. The expression of other proteins, such as inflammatory cytokines, apolipoproteins, and other factors in the head injury cascade are of primary interest for their role in TBI, as well as the association with the subsequent development of AD. This research is conducted in collaboration with the Safar Center for Resuscitation Research and the Brain Trauma Research Center at the University of Pittsburgh, and Cephalon Inc. We are currently using a genetically altered 'knock-in' mouse model of AD to examine the relationship between post-traumatic elevations in caspases, inflammatory cytokines and nuclear transcription factors, with increased amyloid production in a controlled cortical impact paradigm. The experiments are designed to test the hypothesis that interventions attenuating injury-induced overproduction of potentially neurotoxic amyloid will improve neuronal viability and functional recovery after TBI. Dr. DeKosky’s clinical research includes trials of experimental medications for treatment of Alzheimer’s disease and neuroimaging of amyloid in the brains of humans as a biomarker for diagnosis and effectiveness of interventions in AD. He is the principal investigator on a 5 year, 3000 person double blind, placebo controlled trial, funded by the National Center for Complementary and Alternative Medicine of the NIH, to determine if Ginkgo biloba will delay the onset of dementia and Alzheimer’s disease. Projects in the laboratory include: Synapse loss and cholinergic function and structure in normal aging, Alzheimer's disease and mild cognitive impairment. Alpha-1-antichymotrypsin, beta-amyloid, and apolipoprotein metabolism in Alzheimer's disease. Effects of brain trauma on amyloid precursor protein (APP), beta-amyloid, and cholesterol metabolism in human victims of TBI, and in the humanized beta-amyloid mouse model of TBI. Therapeutic effects of moderate hypothermia, cytokine receptor blockade, and other therapeutic interventions on APP metabolism, antioxidant response and functional outcome after experimental brain trauma. Recent Publications Lyketsos, C.G., Lopez, O., Jones, B., Fitzpatrick, A.L., Breitner, J., and DeKosky, S.T. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment. JAMA 288:1475,1483, 2002. Ikonomovic, M.D., Uryu, K., Abrahamson, E.E., Ciallella, J.R., Trojanowski, J.Q., Lee, V.M-Y., Clark, R.S., Marion, D.W., Wisniewski, S.R., DeKosky, S.T. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Experimental Neurology 190:192-203, 2004. DeKosky, S.T., Abrahamson, E.E., Taffe, K.M., Dixon, C.E., Kochanek, P.M., Ikonomovic, M.D. Effects of post-injury hypothermia and nerve growth factor infusion on antioxidant enzyme activity in the rat: Implications for clinical therapies. Journal of Neurochemistry 90:998-1004, 2004. DeKosky, S.T. and Marek, K. Looking backward to move forward: Early detection of neurodegenerative disorders. Science 302:830-834, 2003. Ikonomovic, M.D., Mufson, E.J., Wuu J., Cochran, E.J., Bennett, D.A., and DeKosky, S.T. Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: Correlation with Alzheimer’s neuropathology. Journal of Alzheimer’s Disease 5:39-48, 2003. DeKosky, S.T., Ikonomovic, M.D., Wang, X., Farlow, M., Wisniewski, S., Lopez, O.L., Becker, J.T., Saxton, J., Klunk, W.E., Sweet, R., Kaufer, D.I., and Kamboh, M.I. Plasma and cerebrospinal fluid alpha-1-antichymotrypsin levels in Alzheimer’s disease: Correlation with cognitive impairment. Annals of Neurology 53:81-90, 2003. DeKosky, S.T., Ikonomovic, M.D., Styren, S.D., Beckett, L., Wisniewski, S., Bennett, D., Kordower, J.H., and Mufson, E.J. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Annals of Neurology 51:145-155, 2002.