Neurodegenerative Diseases and CNS Biomarker Discovery

Departments of Neurology and Physiology/Pharmacology


The overall focus of our research is on the neuropathophysiology associated with neurodegenerative disorders. Our research focus has expanded over the years from prion diseases and Alzheimer’s disease (AD) to acute and chronic traumatic brain injury (TBI). The secondary long-term effects of TBI have been identified as a risk factor for the group of diseases termed tauopathies which includes, but not limited to, AD, chronic traumatic encephalopathy (CTE) and likely Parkinson's disease. Our research involves biomarker discovery, validation and development of ultrasensitive diagnostic protein biomarker assays. In addition, our studies have included efforts on enhancing neuroprotection and reducing neurodegeneration following acute and chronic TBI using both pharmacological and molecular approaches as a means of therapeutic intervention.

Below is a partial list of our current funding reflecting some of our research interests:

Biomarker Based Precision Medicine Approach to TBI Subphenotypes

Funding Source: Department of Defense

Project Summary

To examine and characterize the temporal profile of a panel of biofluid biomarker
candidates from three cohorts: University of Pittsburgh, Baylor College of Medicine and the Malcolm Randal VA medical center. The key markers are precision medicine and TBI-subphenotype-based, and include neuronal/astroglia injury (UCH-L1, GFAP), axonal injury (NF-L, pNF-H), neurodegeneration (T-tau, P-tau231, alpha-synuclein), proinflammatory response (cytokine IL-6, chemokine ITAC, cytokine receptors sCD30, sIL1RII), vascular injury/remodeling markers (VEGF-A), autoimmunity response (autoantibodies to GFAP, NFL, GAD1, MBP, MAG etc.) and selected HPA axis hormones (cortisol, testosterone , estradiol & T3).

Validation of the Ultrasensitive Laser-Based RCA-SOFIA Platform for Detection of PD Associated alpha-Synuclein Oligomers in Human Blood

Funding Source: Michael J. Fox Foundation

Project Summary

Sensitive, specific and consistent detection of oligomeric alpha synuclein (a-SynO) in biofluids might provide a reliable biomarker for disease diagnosis, progression, and a theranostic approach. The study design for this project includes: (i) a-SynO assay development using a sensitive laser-based immunoassay (RCA-SOFIA) and a commercially available, but "homebrew" required, single molecule array (SIMOA) platform, (ii) Characterizing the analytical metrics associated with in vitro a-SynO detection, (iii) Validating RCA-SOFIA and SIMOA "homebrew" in vivo by detection of a-SynO in stratified PD (and control) patient bloods with and without exosome preparation.

Gap-Based Milieu Biomarkers for Traumatic Brain Injury (GAMBIT-TBI)

Funding Source: Department of Defense

Project Summary

Currently, there exists important and essential unfilled and unanswered clinical
knowledge gaps, especially regarding the heterogeneity of TBI pathology, subphenotypes, and disease progression / recovery course. The GAMBIT-TBI study is to use disruptive thinking and innovation strategies to introduce knowledge gap-filling blood- & neuroimaging-based “milieu” biomarker tools to interrogate TBI subphenotype and prognosticate military and civilian TBI related post-acute cognitive and emotional dysfunctions. GAMBIT-TBI has four interlinked projects: a) Studying panels of CNS biomarkers and correlating them to TBI subphenotypes and cognitive deficits, b) Examining moderators of CNS damage and neurodegeneration, c) Neuroimaging assessment of polytomous mechanisms of brain health decline after TBI, and d) Plasma DNA methylation profiling for TBI interrogation. Integrating the 4 projects will have short-term benefits on individualized patient care post TBI and long-term benefits on follow-up care and treatments.

For More Information Contact:

Richard Rubenstein, Ph.D., Professor and Director