Associate Professor of Neurology
Phone: (412) 383-8900
Specialized Areas of Interest
During the past academic year, Dr. Ikonomovic conducted several research projects, studying alterations in the cholinergic system and neuropathological changes during the progression of Alzheimer’s disease (AD). In the Religious Order Study, Dr. Ikonomovic collaborated with Drs. Steven DeKosky, Lynn Wecker (University of Florida) and Elliott Mufson (Rush University Medical Center, Chicago) on a project examining the status of nicotinic acetylcholine receptor (nAChR) binding in the frontal cortex during AD progression. This study revealed that nAChR binding, known to diminish in end-stage AD, is stable during mild cognitive impairment and mild-moderate AD, but that α4 nAChR receptor binding might be influenced by the presence of amyloid pathology; lower binding levels correlated with more neuritic plaques and greater likelihood of AD by CERAD and NIA/Reagan pathological diagnoses. Dr. Ikonomovic presented this work at the 2005 Society for Neurosciences conference.
Dr. Ikonomovic performed a histological characterization of the amyloid-imaging PET tracer, Pittsburgh Compound-B (PiB), binding to post-mortem human brain tissue from the AN-1792 immunotherapy trial in AD patients. This study, in collaboration with Drs. DeKosky, William Klunk (Psychiatry) and Chester Mathis (Radiology), found that the brains of immunized patients were remarkable for a focal absence of amyloid-β (Aβ) plaques and for decreased PIB binding levels, which correlated with reduced amyloid load. The study indicated that pre- and post-treatment amyloid imaging using PIB PET in vivo would be able to detect changes in brain amyloid produced by immunotherapies. Dr. Ikonomovic also characterized binding patterns of the X-34 (a highly fluorescent amyloid-binding compound) in AD brains. This work was published in a book chapter. Dr. Ikonomovic also performed histological characterization of 6-CN-BTA-1 (a highly fluorescent derivative of PiB) binding to Aβ plaques in AD brains. This study demonstrated that 6-CN binds preferentially to compact neuritic Aβ plaques, suggesting its affinity for binding to aggregated Aβ. This work aided in interpreting the binding properties of PIB, currently under evaluation as a diagnostic marker in AD patients. Dr. Ikonomovic presented these results at the 2005 Alzheimer’s Association Conference on Prevention of Dementia.
Dr. Ikonomovic also conducted a study examining the relationship between changes in glutathione-S-transferase (GST) protein and amyloid-beta (Aβ) peptide levels in the temporal cortex from subjects with AD or with severe traumatic brain injury. This study was in collaboration with Drs. DeKosky and Ilyas Kamboh (Human Genetics), and the Brain Trauma Research Center at the University of Pittsburgh. It revealed that lower GSTM1-1 levels are associated with higher Aβ levels and plaque deposition. This finding may reflect dysfunction or reduction in GST activity in patients with higher Aβ load, exacerbation of oxidative stress mediated secondary injury, and worsened long term outcome. Dr. Ikonomovic presented these results at the 2006 American Academy of Neurology meeting.
In the next academic year, the work will continue on collecting new data and publishing results of these studies. In addition, several new projects will be initiated to examine whether interventions with NMDA antagonists could attenuate neurological deficits associated with neuronal injury following severe brain trauma, and to examine the effects of small molecule Aβ-binding agents as a potential anti-amyloid therapy intervention.
Dr. Ikonomovic's publications can be reviewed through the National Library of Medicine's publication database.
Professional Organization Membership
Society for Neuroscience
International Brain Research Organization
New York Academy of Sciences
National Neurotrauma Society