Department of Chemistry team studies Alzheimer's disease
Sunday, June 22, 2014
Department of Chemistry team studies Alzheimer's diseaseAlzheimer’s disease is a devastating form of dementia . Several hypotheses exist to explain the cause of Alzheimer’s disease. One is that the tau protein, which stabilizes microtubules, forms neurofibrillary tangles inside nerve cells. If this hypothesis is correct, then a sensor that detects the tau protein could be an important technique to provide early diagnosis of Alzheimer’s disease.
In the June 7, 2014 issue of the journal Analyst, an Oakland University team led by Assistant Professor Senela Martic, of the Department of Chemistry, published a report about a protein-based electrochemical biosensor for detection of tau protein, a neurodegenerative disease biomarker (Volume 139, Pages 2823-2831). Lead author is Biomedical Sciences: Health and Environmental Chemistry graduate student Jose Esteves-Villanueva, and a coauthor is undergraduate Hanna Trzeciakiewicz, current holder of the Michael P. and Elizabeth A. Kenny Merit Scholarship for the Sciences. The abstract is reproduced below.
A protein-based electrochemical biosensor was developed for detection of tau protein aimed towards electrochemically sensing misfolding proteins. The electrochemical assay monitors tau-tau binding and misfolding during the early stage of tau oligomerization. Electrochemical impedance spectroscopy was used to detect the binding event between solution tau protein and immobilized tau protein (tau-Au), acting as a recognition element. The charge transfer resistance (R-ct) of tau-Au was 2.9 +/- 0.6 k Omega. Subsequent tau binding to tau-Au decreased the R-ct to 0.3 + 0.1 k Omega (90 + 3% decrease) upon formation of a tau-tau-Au interface. A linear relationship between the Rct and the solution tau concentration was observed from 0.2 to 1.0 mu M. The Rct decrease was attributed to an enhanced charge permeability of the tau-tau-Au surface to a redox probe [Fe(CN)(6)](3/4) . The electrochemical and surface characterization data suggested conformational and electrostatic changes induced by tau-tau binding. The protein-based electrochemical platform was highly selective for tau protein over bovine serum albumin and allowed for a rapid sample analysis. The protein-based interface was selective for a non-phosphorylated tau441 isoform over the paired-helical filaments of tau, which were composed of phosphorylated and truncated tau isoforms. The electrochemical approach may find application in screening of the early onset of neurodegeneration and aggregation inhibitors.